NSAIDs, or nonsteroidal anti-inflammatory drugs, are a class of medications that reduce pain, lower fevers, and fight inflammation. They’re among the most widely used medicines in the world, available both over the counter (ibuprofen, naproxen, aspirin) and by prescription. The name “nonsteroidal” simply distinguishes them from corticosteroids, which also reduce inflammation but work in a completely different way.
How NSAIDs Work in Your Body
Your body produces chemicals called prostaglandins at sites of injury or infection. Prostaglandins trigger inflammation, amplify pain signals, and raise your body temperature. NSAIDs block the enzyme responsible for making these chemicals, called cyclooxygenase, or COX. By shutting down prostaglandin production, NSAIDs reduce swelling, dull pain, and bring down fevers.
There are two versions of the COX enzyme. COX-2 ramps up during injury and drives inflammation, which is the target you actually want to hit. COX-1, on the other hand, runs all the time and serves protective roles, particularly in the stomach lining and kidneys. Most common NSAIDs block both versions, which is why they work well for pain but can cause side effects in the gut. Some prescription NSAIDs were designed to primarily block COX-2 while leaving COX-1 alone, reducing stomach problems, though these carry their own risks.
Common Over-the-Counter NSAIDs
The three NSAIDs you can buy without a prescription are the ones most people reach for:
- Ibuprofen (Advil, Motrin) is effective for headaches, muscle pain, menstrual cramps, toothaches, earaches, arthritis, and fever. It works relatively quickly but needs to be taken every six to eight hours.
- Naproxen (Aleve) covers similar territory: arthritis, headaches, muscle strains, menstrual cramps, and fever. Its main advantage is a longer duration of action, so you take fewer doses per day.
- Aspirin (Bayer) is used for minor aches and pains, but its most distinctive role is heart protection. In low doses (81 mg), aspirin helps prevent heart attacks and strokes by reducing blood clotting, a property the other NSAIDs don’t reliably share.
Prescription NSAIDs
When over-the-counter options aren’t strong enough, doctors may prescribe higher-potency NSAIDs. Common examples include celecoxib (Celebrex), diclofenac (Voltaren), indomethacin (Indocin), and ketorolac (Toradol). Celecoxib is the most well-known COX-2 selective NSAID, meaning it targets the inflammation enzyme more precisely and tends to cause fewer stomach problems than traditional NSAIDs. Ketorolac is typically reserved for short-term use after surgery or acute injuries because of its potency.
Topical NSAIDs: Gels, Creams, and Patches
Not all NSAIDs come as pills. Topical versions, most commonly diclofenac gel, are applied directly to the skin over a painful joint or muscle. Only about 5% of a topical NSAID enters the bloodstream, compared to the full dose from a pill. Despite that low absorption, meta-analyses have found that topical NSAIDs provide similar pain relief to oral versions for both chronic osteoarthritis and acute muscle or joint injuries. In clinical data, topical diclofenac improved pain by 50% within one week for acute sprains and strains.
The tradeoff is straightforward: topical NSAIDs cause far fewer stomach and systemic side effects, while the most common complaints are mild skin reactions like dryness or itching at the application site. One study found that switching patients from oral to topical NSAIDs reduced severe gastrointestinal side effects from 26% to 17%. For localized pain in the hands or knees, a topical NSAID is often a smarter first choice.
Stomach and Digestive Side Effects
The most common downside of oral NSAIDs is what they do to your stomach. Because these drugs block COX-1 alongside COX-2, they strip away the protective mucus layer that lines your digestive tract. The result ranges from mild heartburn to serious ulcers. Among chronic NSAID users, 5% to 22% develop gastric or duodenal ulcers. Even short-term use isn’t harmless: studies show that 60% to 100% of patients taking NSAIDs for just one to two weeks develop at least minor damage like superficial erosions or increased blood loss in the stool, though most of these changes cause no symptoms.
Your risk of stomach problems goes up with higher doses, longer use, older age, and if you’re also taking blood thinners or corticosteroids. Taking NSAIDs with food or using a stomach-protecting medication can help, but it doesn’t eliminate the risk entirely.
Cardiovascular Risks
All non-aspirin NSAIDs carry an FDA boxed warning, the most serious type, for increased risk of heart attack and stroke. This applies to both over-the-counter and prescription versions. The risk can appear as early as the first weeks of treatment and increases with higher doses and longer use. People who already have heart disease face the greatest absolute danger, but the relative increase in risk applies even to people without known heart problems.
Aspirin is the exception here. In low doses, it actually protects against cardiovascular events, which is why many people take a daily baby aspirin on their doctor’s recommendation. But ibuprofen, naproxen, and prescription NSAIDs do not offer this benefit and may work against it.
Who Should Avoid NSAIDs
Certain groups need to be particularly careful. The FDA specifically warns against using NSAIDs at 20 weeks of pregnancy or later. At that stage, the baby’s kidneys produce most of the amniotic fluid, and NSAIDs can impair kidney function in the developing baby, leading to dangerously low fluid levels. At around 30 weeks, NSAIDs can also cause heart problems in the baby. The one exception is low-dose aspirin (81 mg), which is sometimes used during pregnancy for specific conditions under medical supervision.
People with kidney disease are also at elevated risk because NSAIDs reduce blood flow to the kidneys. Those with a history of stomach ulcers or gastrointestinal bleeding face obvious dangers from a drug class that weakens the stomach lining. And some people with asthma experience worsening symptoms or severe reactions triggered by NSAIDs, a condition sometimes called aspirin-exacerbated respiratory disease.
How NSAIDs Compare to Acetaminophen
Acetaminophen (Tylenol) is often grouped with NSAIDs in people’s minds, but it works differently and is not an NSAID. Acetaminophen reduces pain and fever but does very little for inflammation. This means it won’t help much with a swollen, inflamed joint, but it also won’t cause stomach ulcers or raise cardiovascular risk the way NSAIDs do. If your pain doesn’t involve significant inflammation, acetaminophen may be the safer choice. If swelling is a major part of the problem, an NSAID will typically work better.
Using NSAIDs Safely
The general principle with NSAIDs is simple: use the lowest effective dose for the shortest time that handles your symptoms. For occasional headaches or a pulled muscle, a few days of ibuprofen or naproxen is unlikely to cause problems for most people. Chronic daily use is where the risks accumulate, particularly for your stomach, kidneys, and heart.
If you need long-term pain management for something like arthritis, topical NSAIDs are worth considering for accessible joints like hands and knees. They deliver comparable pain relief with a fraction of the systemic exposure. For deeper or more widespread pain, the choice between an oral NSAID and other approaches depends on your individual risk profile, something worth a real conversation rather than a default reach for the medicine cabinet.