NSAIDs, or nonsteroidal anti-inflammatory drugs, are a class of pain relievers that reduce inflammation, ease pain, and lower fevers. The most common ones you’ll recognize are ibuprofen (Advil, Motrin), naproxen (Aleve), and aspirin (Bayer). But the full list extends well beyond those three, with more than a dozen prescription-strength options available.
Over-the-Counter NSAIDs
Three NSAIDs are widely available without a prescription in the United States:
- Ibuprofen (sold as Advil and Motrin): up to 1,200 mg per day in OTC doses, typically one to two 200 mg tablets every four to six hours.
- Naproxen sodium (sold as Aleve): up to 660 mg per day in OTC doses, typically one to two 220 mg tablets every 8 to 12 hours. Prescription doses can go as high as 1,500 mg daily.
- Aspirin (sold as Bayer and St. Joseph): up to 4,000 mg per day, typically one to two 325 mg tablets every four hours.
These three cover the vast majority of what people buy for headaches, muscle aches, menstrual cramps, and minor injuries. Ibuprofen and naproxen are the most popular choices for general pain and inflammation. Aspirin has a unique role that sets it apart from the rest of the class, which we’ll get to below.
Prescription NSAIDs
When OTC options aren’t enough, doctors can prescribe stronger or more specialized NSAIDs. The FDA-approved list includes diclofenac, meloxicam, indomethacin, ketorolac, ketoprofen, etodolac, piroxicam, sulindac, nabumetone, diflunisal, flurbiprofen, mefenamic acid, oxaprozin, fenoprofen, and tolmetin. Higher-dose versions of ibuprofen and naproxen are also available by prescription.
One prescription NSAID stands in its own category: celecoxib (Celebrex). It’s a selective COX-2 inhibitor, meaning it targets inflammation more narrowly than the others. Two other selective COX-2 inhibitors, rofecoxib (Vioxx) and valdecoxib (Bextra), were pulled from the market after evidence showed they significantly increased the risk of heart attacks and strokes.
How NSAIDs Work
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 enzymes (called COX-1 and COX-2) that produce these chemicals. By cutting off prostaglandin production, they reduce swelling, relieve pain, and bring down fevers.
Most NSAIDs block both COX-1 and COX-2. COX-2 ramps up during injury and inflammation, so blocking it is what provides pain relief. COX-1, on the other hand, does useful things all the time, like protecting the stomach lining and supporting kidney function. This is why NSAIDs can cause stomach problems: they’re blocking a protective enzyme as a side effect of blocking the inflammatory one. Celecoxib was designed to target COX-2 more precisely and spare COX-1, which is why it tends to be gentler on the stomach.
What Makes Aspirin Different
Aspirin is technically an NSAID, but it behaves differently from every other drug in the class. While all NSAIDs temporarily block COX enzymes, aspirin permanently disables them. This matters most for blood clotting. Platelets, the tiny blood cells that form clots, rely on COX-1 to function. Aspirin knocks out their COX-1 for good, and since platelets can’t repair themselves, the anticlotting effect lasts for the entire lifespan of those cells (about 7 to 10 days). Other NSAIDs only suppress clotting while the drug is active in your system.
This permanent effect is why low-dose aspirin (81 mg) is used to prevent heart attacks and strokes in people with cardiovascular disease. No other NSAID is used this way. It’s also worth knowing that ibuprofen can interfere with aspirin’s anticlotting action if taken at the wrong time. Ibuprofen can physically block aspirin from reaching the enzyme, so if you take both, aspirin needs to be taken first.
One important safety note for parents: aspirin should not be given to children or teenagers, especially during flu or chickenpox. It’s been linked to Reye’s syndrome, a rare but serious condition affecting the brain and liver. Ibuprofen and acetaminophen are safe alternatives for kids. Aspirin can also appear in products you might not expect, like Alka-Seltzer, sometimes listed as acetylsalicylic acid or salicylate.
NSAIDs vs. Acetaminophen
Acetaminophen (Tylenol) is not an NSAID, and the distinction matters. Both relieve pain and reduce fevers, but acetaminophen does not treat inflammation. It works only in the brain and spinal cord, raising your pain threshold so you feel less discomfort. NSAIDs work throughout the body, directly reducing swelling and inflammation at the site of an injury or irritation.
If your pain involves inflammation, like a sprained ankle, arthritis flare, or a swollen joint, an NSAID will generally work better. For a headache or a fever without significant inflammation, acetaminophen may be equally effective with a different side-effect profile. Acetaminophen is processed by the liver rather than affecting the stomach or kidneys, so the risks are different rather than simply lower.
Risks and Side Effects
All non-aspirin NSAIDs carry FDA-required warnings about two major risks: cardiovascular events and gastrointestinal bleeding. The risk of heart attack or stroke increases with higher doses and longer use, and it exists even in people without prior heart problems. Stomach and intestinal bleeding can happen without warning symptoms, particularly in older adults or people who take NSAIDs frequently.
NSAIDs can also affect kidney function. They reduce blood flow to the kidneys by blocking prostaglandins that help regulate it. For most people taking an occasional dose, this isn’t a concern. But regular use, especially in people with existing kidney issues or dehydration, can cause problems.
During pregnancy, the FDA recommends avoiding all NSAIDs from 20 weeks onward. After 20 weeks, the developing baby’s kidneys produce most of the amniotic fluid, and NSAIDs can impair fetal kidney function, leading to dangerously low fluid levels. After 30 weeks, NSAIDs carry the additional risk of causing premature closure of a blood vessel in the baby’s heart. The one exception is low-dose aspirin (81 mg), which is sometimes prescribed for specific pregnancy-related conditions.
Choosing the Right NSAID
For most people reaching for something in their medicine cabinet, the practical choice comes down to ibuprofen or naproxen. Ibuprofen acts faster and wears off sooner, so it’s well suited for short-lived pain that you want quick relief from. Naproxen lasts longer (8 to 12 hours per dose versus 4 to 6 for ibuprofen), making it more convenient for ongoing pain like a sore back or menstrual cramps where you don’t want to keep re-dosing.
Prescription NSAIDs like meloxicam and diclofenac are typically reserved for chronic conditions such as osteoarthritis or rheumatoid arthritis, where daily management is needed and a doctor can monitor for side effects over time. Celecoxib is often chosen when someone needs long-term NSAID therapy but has a history of stomach problems, since its selective mechanism is less likely to irritate the GI tract.