Ibuprofen and naproxen have long been thought as the better pain relievers, but a study comparing them to celecoxib found surprising results A clinical trial is now investigating this in people who take high doses of celecoxib (Celebrex), ibuprofen, or naproxen for arthritis pain. The results won't be available until at least 2016. The results won't be available until at least 2016. Naming the universal “safest” NSAID deems difficult because each NSAID has its own different adverse reaction profile; “safety” priorities shoul d be individualized based upon patient’s concurrent illnesses. This review will discuss the potential adverse reactions of both conventions (non-selective) and selective NSAIDs according to specific organ systems. Cardiovascular effect. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) which are widely used in clinical practice are also very well-known for their various adverse reactions. In this case, a reasonable question is which NSAID is the safest? The answer to this question, it turns out, depends as much on how you use the NSAID as which one you choose. The answer to this question, it turns out, depends as much on how you use the NSAID as which one you choose. The authors conclude that the vascular risks of diclofenac and possibly ibuprofen are comparable to coxibs, whereas high-dose naproxen is associated with less vascular. And if your pain continues for more than a 10 days or isn’t controlled by the OTC NSAID, it’s a good idea to talk with your doctor. WebMD Feature Reviewed by Michael W. Smith, MD on June 18, 2013 Because many medicines available over the counter contain aspirin or other drug classes similar to naproxen (such as ibuprofen or ketoprofen), if you take certain products together you may accidentally take too much and be at risk of overdose. Lowest effective dose of ibuprofen or naproxen (or other generic NSAID) plus a stomach acid reducer Celecoxib, with or without a proton pump inhibitor Topical NSAID If you have a history of ulcers, drink heavily, are older, or take steroids for asthma or rheumatoid arthritis, a standard NSAID like aspirin or ibuprofen may put you at higher risk of.