BACKGROUND: Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with increased cardiovascular morbidity and mortality. The purpose of this study was to examine the effect of ongoing NSAID treatment at time of admission for myocardial infarction (MI) on prognosis. METHODS: All patients admitted with first-time MI in 1997-2006 were included by use of individual-level linkage of nationwide registries. By claimed prescription of NSAIDs, availability of tablets was estimated within 14days prior to inclusion and defined ongoing use. Risk of death within 30days and risk of death or MI within 1year was analyzed by logistic regression and Cox proportional-hazard models, respectively. RESULTS: A total of 97,458 patients were included (mean age 69.9 [SD 13.2] years and 62% males); the 30day and 1year mortality rates were 18.1% and 27.7%, respectively. Ongoing NSAID treatment was identified in 12,156 (12.5%) patients and 30-day mortality was significantly increased in patients receiving rofecoxib (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.22-1.68) and celecoxib (OR 1.23; CI 1.03-1.47) relative to no use of NSAIDs. Correspondingly, the 1-year rate of death or recurrent MI was significantly increased in patients receiving rofecoxib (hazard ratio [HR] 1.15; CI 1.04-1.27), celecoxib (HR 1.13; CI 1.01-1.26), diclofenac (HR 1.12; CI 1.04-1.20) or any NSAID use (HR 1.05; CI 1.02-1.09). No association was found for naproxen or ibuprofen. CONCLUSION: Ongoing treatment with NSAIDs and in particular the cyclooxygenase-2-selective inhibitors rofecoxib, celecoxib, and diclofenac is associated with worsened prognosis in patients admitted with first-time MI.