Rofecoxib (Vioxx), the first COX-2 selective non-steroidal anti-inflammatory drug (NSAID), was recently withdrawn by Merck Sharp & Dohme. Indeed, both observational studies and randomised clinical trials showed that rofecoxib is associated with a significantly increased risk of acute myocardial infarction in patients receiving either high daily dosage (>25 mg/day) or for a long period of time (> 18 months). The precise mechanism responsible for this phenomenon still remains unknown. Currently available data suggest that this adverse effect is not observed with other COX-2 NSAIDs, especially celecoxib for which the information is most abundant. Nevertheless, caution is required because of lack of prospective long-term data, and strict respect of indications and modalities of clinical use of COX-2 NSAIDs is mandatory. Finally, in patients with high cardiovascular risk who should receive a COX-2 selective NSAID, the association with a low dose of acetylsalicylic acid is recommended in order to benefit of a protective antiplatelet effect.