Since selective cyclooxygenase-2 inhibitors (coxibs) entered the market, there has been concern about the cardiovascular safety of coxibs. In addition, recent data suggest that classical non-steroidal anti-inflammatory drugs (NSAIDs) have a similar cardiovascular risk. Importantly, all of the clinical trials with NSAIDs and coxibs so far were not purpose-designed to specifically and prospectively address cardiovascular safety and were clearly underpowered to detect any meaningful differences. In this current uncertainty about safety of NSAIDs and coxibs, the definitive answer as to the net effect of coxibs and NSAIDs on cardiovascular events can only be provided by well designed adequately powered, long-term clinical trials, which is now under way.