STUDY OBJECTIVE:To assess theriskof long-term use of fivenonsteroidal antiinflammatory drugs(NSAIDs)--rofecoxib, celecoxib, ibuprofen, naproxen, and diclofenac--in relation toacutemyocardial infarction.DESIGN:Five separate nested case-control studies, one for each NSAID, designed to minimize important biases present in other observational studies. Setting. University-affiliated research program. Data Source. The United Kingdom General Practice Research Database (GPRD).MEASUREMENTS AND MAIN RESULTS:We identified all people in the GPRD aged 30-79 years who had a first recorded prescription for rofecoxib, celecoxib, ibuprofen, naproxen, or diclofenac after January 1, 1999. Cases of newly diagnosed, first-timeacutemyocardial infarctionwere then identified from the study population, along with matched control subjects. Relativeriskestimates foracutemyocardial infarctioninpatientswith no recordedmajorclinicalrisk factorsforacutemyocardial infarctionwere determined for each NSAID according to receipt of 2-4, 5-9, 10-19, or 20 or more prescriptions compared with receipt of only 1 prescription. Results were adjusted for relevant variables possibly related to theriskforacutemyocardial infarction. No material elevation ofriskaccording to the number of prescriptions received for ibuprofen or naproxen was noted. However, a substantial increasedrisksimilar to that found in clinical trials was noted inpatientswho received 10 or more prescriptions for rofecoxib, celecoxib, or diclofenac.CONCLUSION:Extensive use of rofecoxib, celecoxib, and diclofenac increases theriskofacutemyocardial infarction, but similar use of ibuprofen and naproxen does not.