Conventional nonsteroidal antiinflammatory drugs (NSAIDs) are associated with acute renal failure, but cyclooxygenase-2 inhibitors have not been comparatively evaluated. The authors conducted a nested case-control study to assess the association between exposure to NSAIDs, including cyclooxygenase-2 inhibitors, and hospitalization for acute renal failure. They identified 121,722 new NSAID users older than age 65 years from the administrative health care databases of Quebec, Canada, in 1999-2002. Data for 4,228 cases and 84,540 controls matched on age and follow-up time were analyzed by using conditional logistic regression, adjusted for sex, age, health status, health care utilization measures, exposure to contrast agents, and nephrotoxic medications. The risk of acute renal failure for all NSAIDs combined was highest within 30 days of treatment initiation (adjusted rate ratio (RR) = 2.05, 95% confidence interval (CI): 1.61, 2.60) and receded thereafter. The association with acute renal failure within 30 days of therapy initiation was comparable for rofecoxib (RR = 2.31, 95% CI: 1.73, 3.08), naproxen (RR = 2.42, 95% CI: 1.52, 3.85), and nonselective, non-naproxen NSAIDs (RR = 2.30, 95% CI: 1.60, 3.32) but was borderline lower for celecoxib (RR =1.54, 95% CI: 1.14, 2.09; test for interaction comparing celecoxib with rofecoxib, p = 0.057). There was a significant association for both selective and nonselective NSAIDs with acute renal failure, but confirmatory studies are required.