NSAIDs, or nonsteroidal anti-inflammatory drugs, are a class of medications that reduce pain, lower fever, and fight inflammation. They’re among the most widely used drugs in the world, and you’ve almost certainly taken one: ibuprofen (Advil, Motrin), naproxen (Aleve), and aspirin (Bayer) are all NSAIDs available over the counter. Prescription-strength versions treat more severe conditions like arthritis and post-surgical pain.
How NSAIDs Work in Your Body
When tissue in your body is damaged or irritated, it produces chemicals called prostaglandins. These chemicals trigger inflammation, amplify pain signals, and raise your body temperature. NSAIDs block the enzymes (called COX-1 and COX-2) responsible for making prostaglandins, which is why a single ibuprofen tablet can simultaneously ease a headache, bring down a fever, and reduce the swelling around a sprained ankle.
Not all NSAIDs block these enzymes in the same way. Aspirin permanently disables them, which is partly why low-dose aspirin has a lasting effect on blood clotting. Ibuprofen and most other NSAIDs block the enzymes temporarily and reversibly, so their effects wear off as the drug leaves your system.
Common Over-the-Counter and Prescription NSAIDs
Three NSAIDs are widely available without a prescription:
- Ibuprofen (Advil, Motrin): shorter-acting, typically taken every 4 to 6 hours
- Naproxen sodium (Aleve): longer-acting, usually taken every 8 to 12 hours
- Aspirin (Bayer): also used in low doses for heart protection
When OTC options aren’t strong enough, prescription NSAIDs offer higher doses or different formulations. Common prescription NSAIDs include celecoxib (Celebrex), diclofenac (Voltaren), indomethacin (Indocin), fenoprofen (Nalfon), and ketorolac (Toradol). Celecoxib is notable because it selectively targets the COX-2 enzyme, which was designed to reduce stomach-related side effects compared to older NSAIDs.
What NSAIDs Treat
NSAIDs are used for a broad range of pain and inflammatory conditions. They’re a first-line choice for headaches, menstrual cramps, toothaches, muscle strains, sprains, and minor injuries. For chronic conditions, they help manage the pain and swelling of osteoarthritis and rheumatoid arthritis. They also reduce fever from infections and illness.
Because they actively reduce inflammation rather than just dulling pain, NSAIDs are particularly effective when swelling is part of the problem. A twisted knee, an inflamed joint, or a sore back after overexertion will generally respond better to an NSAID than to a pain reliever that doesn’t target inflammation.
NSAIDs vs. Acetaminophen
Acetaminophen (Tylenol) is often grouped with NSAIDs because it also treats pain and fever, but it works differently. Both drugs are thought to block prostaglandin production, but acetaminophen only does this in the central nervous system. NSAIDs work in the brain and throughout the body, which is why they reduce inflammation at the site of an injury while acetaminophen does not.
This distinction matters when choosing between them. If you have a headache or a mild fever, either one can help. If you’re dealing with swelling from a sprain, arthritis flare, or any condition involving visible inflammation, an NSAID is the better choice. On the other hand, acetaminophen tends to cause fewer stomach problems, so it may be preferable for people who are sensitive to NSAIDs or need to avoid them for other reasons.
Side Effects and Risks
NSAIDs carry an FDA boxed warning, the most serious safety alert the agency issues, for two categories of risk: cardiovascular events and gastrointestinal harm.
On the cardiovascular side, NSAIDs increase the risk of heart attack and stroke. This risk can appear early in treatment and may grow with longer use. A large meta-analysis found a 42% relative increase in serious vascular events among users of COX-2 selective NSAIDs compared to placebo. People with existing heart disease face the highest danger, and NSAIDs are specifically prohibited after coronary artery bypass surgery.
Gastrointestinal problems are the other major concern. NSAIDs can cause bleeding, ulceration, and perforation of the stomach or intestinal lining, and these events can happen at any time during use without warning symptoms. Older adults and anyone with a history of stomach ulcers or GI bleeding face elevated risk. Even among newer formulations designed to be gentler on the stomach, GI side effects still occur in roughly 17% of older patients.
Kidney effects are less well known but still significant. An estimated 1 to 5% of NSAID users develop some degree of kidney-related side effects. About 25% of people taking NSAIDs experience some sodium retention, which can raise blood pressure and worsen heart failure.
Who Should Avoid NSAIDs
The FDA 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. Low amniotic fluid can affect lung, digestive, and muscle development. Low-dose aspirin (81 mg) is an exception and is sometimes prescribed for specific pregnancy-related conditions under medical guidance.
People taking blood thinners should be especially cautious. NSAIDs reduce platelet clumping and can damage the stomach lining, and combining them with anticoagulants significantly increases bleeding risk. In one large clinical trial of patients on blood thinners for atrial fibrillation, adding an NSAID raised the risk of major bleeding by 61% and clinically relevant non-major bleeding by 70%. The combination also doubled the risk of heart failure hospitalization.
Others who face higher risk with NSAIDs include people with kidney disease, uncontrolled high blood pressure, or a history of stomach ulcers. Aspirin-sensitive asthma is another well-known trigger: in susceptible people, NSAIDs can provoke severe breathing difficulty.
Using NSAIDs Safely
For occasional use at OTC doses, NSAIDs are safe for most adults. The risks climb with higher doses and longer durations. If you find yourself reaching for ibuprofen or naproxen daily for more than a week or two, that’s a signal to look into the underlying cause of your pain rather than continuing to manage it with NSAIDs alone.
Taking NSAIDs with food can reduce stomach irritation, though it doesn’t eliminate the risk of more serious GI complications. Staying at the lowest effective dose for the shortest time possible is the most straightforward way to minimize side effects. If you need long-term anti-inflammatory treatment, a prescription NSAID like celecoxib may carry a somewhat lower GI risk, though cardiovascular concerns remain.