NSAIDs, short for nonsteroidal anti-inflammatory drugs, are one of the most widely used classes of medication in the world. They reduce pain, lower fever, and fight inflammation. The most familiar examples are ibuprofen (Advil, Motrin), naproxen (Aleve), and aspirin. You’ve almost certainly taken one.
The “nonsteroidal” part of the name simply means these drugs aren’t steroids, which are a different category of anti-inflammatory medication. NSAIDs work through an entirely different mechanism, and understanding how they do their job helps explain both their benefits and their risks.
How NSAIDs Work in Your Body
Your body produces chemicals called prostaglandins whenever tissue is damaged or irritated. Prostaglandins trigger inflammation, amplify pain signals, and raise your body temperature. NSAIDs block the enzyme responsible for making prostaglandins, called cyclooxygenase (COX). Less prostaglandin production means less swelling, less pain, and lower fever.
There are two versions of this enzyme. COX-1 runs all the time and handles useful housekeeping tasks: it helps protect the lining of your stomach from digestive acids, supports normal kidney blood flow, and helps your blood clot properly. COX-2, on the other hand, ramps up specifically during injury or inflammation. It’s the one you actually want to shut down when you’re in pain.
Most common NSAIDs, like ibuprofen and naproxen, block both COX-1 and COX-2 without much discrimination. That’s why they’re called “nonselective.” They reduce inflammation effectively, but they also interfere with the protective functions COX-1 provides. This tradeoff is the root cause of most NSAID side effects.
Common NSAIDs You’ll Find Over the Counter
The NSAIDs most people encounter without a prescription are ibuprofen (sold as Advil or Motrin), naproxen (sold as Aleve), and aspirin. Ibuprofen and naproxen are the go-to choices for general pain and inflammation. Aspirin occupies a unique role because it irreversibly disables the COX enzyme in platelets, which is why low-dose aspirin is sometimes used for heart protection rather than pain relief.
Prescription NSAIDs include celecoxib (Celebrex), which is a COX-2 selective inhibitor, meaning it targets the inflammation enzyme while largely leaving the stomach-protective enzyme alone. Diclofenac is another prescription option that also comes in a topical gel, useful for joint pain and soft-tissue injuries where you want the drug working locally rather than circulating through your entire system. There are over 20 different NSAIDs available in total.
What NSAIDs Treat
NSAIDs are approved to treat three broad categories: pain, inflammation, and fever. In practice, this covers a wide range of everyday problems. They’re commonly used for muscle pain, menstrual cramps, arthritis (both osteoarthritis and rheumatoid arthritis), gout flares, migraines, and general aches from colds or flu. Topical formulations work well for ankle sprains, tendon inflammation, and soft-tissue injuries.
This is where NSAIDs differ most clearly from acetaminophen (Tylenol). Both reduce pain and fever, but acetaminophen does not reduce inflammation. For conditions driven by inflammation, such as a swollen joint or a sprained ankle, NSAIDs are generally more effective because they address the underlying process causing the pain, not just the pain signal itself.
Stomach and Digestive Risks
Because nonselective NSAIDs block COX-1, they reduce the protective mucus layer that shields your stomach and intestines from their own digestive acids. This is why stomach irritation is the most common side effect, and why long-term or high-dose use can lead to ulcers or gastrointestinal bleeding.
Not everyone faces the same level of risk. The factors that increase your chances of GI complications include being 65 or older, having a history of peptic ulcers, taking blood thinners or corticosteroids at the same time, having an H. pylori infection, using high doses, and taking NSAIDs chronically rather than for short stretches. Among common NSAIDs, ibuprofen carries a lower relative risk of upper GI bleeding (about 2.7 times baseline) compared to naproxen (about 5.6 times baseline). COX-2 selective inhibitors like celecoxib have the lowest GI risk at roughly 1.9 times baseline.
Taking NSAIDs with food can ease mild stomach discomfort, though it doesn’t eliminate the deeper risk of ulceration with prolonged use.
Heart and Cardiovascular Concerns
All non-aspirin NSAIDs carry an FDA boxed warning for increased risk of heart attack and stroke. This applies to both over-the-counter and prescription versions, and to both nonselective and COX-2 selective types. The risk can begin within the first weeks of regular use and tends to increase with higher doses and longer duration.
People who already have heart disease or risk factors for it face a higher absolute risk, though the relative increase applies to everyone. The practical takeaway is straightforward: use the lowest dose that works for the shortest time you need it. NSAIDs are also not to be used after coronary artery bypass surgery, where clinical trials showed a clear increase in heart attacks and strokes in the days following the procedure.
Effects on the Kidneys
Your kidneys rely on prostaglandins to maintain proper blood flow, especially when your body is under stress from dehydration, heart failure, or other conditions that reduce circulation. NSAIDs suppress those prostaglandins, which can reduce blood flow to the kidneys and impair their filtering ability.
For most healthy people using NSAIDs occasionally, kidney effects aren’t a concern. The risk becomes meaningful for people with existing kidney disease. Those with mild kidney disease (stages 1-2) can generally use NSAIDs similarly to people with healthy kidneys. For moderate kidney disease (stage 3), short courses of five days or less are considered acceptably safe. For advanced kidney disease (stage 4), NSAID use requires careful individual assessment, low doses, and close monitoring.
Drug Interactions to Know About
NSAIDs interact meaningfully with several common medications. The most important interaction is with blood thinners: combining NSAIDs with anticoagulants significantly raises the risk of bleeding. Patients on dual antiplatelet therapy after a heart attack who also take an NSAID face roughly double the risk of GI bleeding.
NSAIDs can also raise lithium levels in people taking that medication for mood disorders, potentially pushing it into a toxic range. They can reduce the effectiveness of blood pressure medications. And combining NSAIDs with corticosteroids increases the risk of stomach ulcers beyond what either drug causes alone. Taking two different NSAIDs together offers no benefit and simply increases toxicity.
Aspirin and Children
One NSAID-specific safety rule deserves its own mention: aspirin should not be given to children or teenagers. It has been linked to Reye’s syndrome, a rare but serious condition that causes swelling in the liver and brain, particularly when given during viral illnesses like the flu or chickenpox. Ibuprofen and acetaminophen are safe alternatives for fever and pain in children. Aspirin sometimes appears under other names on labels, including acetylsalicylic acid, acetylsalicylate, salicylic acid, and salicylate, so checking ingredient lists matters.
The exception is children with specific chronic conditions like Kawasaki disease, where aspirin therapy may be prescribed under medical supervision with up-to-date vaccinations against flu and chickenpox.
Choosing the Right NSAID
For occasional pain or a short-term injury, ibuprofen is a reasonable first choice. It has a relatively lower GI risk among nonselective NSAIDs and a long track record. Naproxen lasts longer per dose, making it convenient for all-day relief, but carries somewhat higher GI risk. Celecoxib is the gentlest on the stomach but requires a prescription and comes with the same cardiovascular warnings as other NSAIDs.
Topical NSAIDs, like diclofenac gel, are worth considering for localized pain in joints or soft tissue. They deliver the drug directly where it’s needed with far less systemic exposure, which means fewer concerns about your stomach, kidneys, or cardiovascular system. For pain without significant inflammation, acetaminophen may be sufficient and avoids NSAID-related risks entirely.