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COX inhibitors have analgesic and anti\u2010inflammatory effects, but also increase risks for gastrointestinal ulcers, bleeding, and renal and cardiovascular adverse events. Identification of two isoforms of COX, COX\u20101 and COX\u20102, led to the development of selective COX\u20102 inhibitors, which were launched as having fewer gastrointestinal side effects since gastroprotective prostaglandins produced via COX\u20101 are spared. The balance between COX\u20101 mediated prothrombotic thromboxane and COX\u20102 mediated antithrombotic prostacyclin is important for thrombotic risk. An increased risk of suffering myocardial infarction and death with COX\u20102 inhibitor treatment is well established from clinical trials and observational research. Rofecoxib (Vioxx) was withdrawn from the market for this reason, but the equally COX\u20102 selective etoricoxib has replaced it in Europe but not in the United States. The \u201ctraditional\u201d NSAID diclofenac is as COX\u20102 selective as celecoxib and increases cardiovascular risk dose dependently. COX inhibitor dosages should be lower in osteoarthritis than in rheumatoid arthritis. Randomized trials comparing COX\u20102 inhibitors with NSAIDs have exaggerated their gastrointestinal benefits by using maximal NSAID doses regardless of indication, and\/or hidden the cardiovascular risk by comparing with COX\u20102 selective diclofenac instead of low\u2010dose ibuprofen or naproxen. Observational studies show increased cardiovascular risks within weeks of treatment with COX\u20102 inhibitors and high doses of NSAIDs other than naproxen, which is the safest alternative. 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