Background: Studies have postulated that cyclooxygenase-2(COX-2) selective inhibitors affect cardiovascular risk through various mechanisms. Some of these mechanisms could increase risk(for example, inhibition of prostacyclin production), and some could decrease risk(for example, inhibition of inflammation). Objective: To determine the effect of COX-2 inhibitors on risk for nonfatal myocardial infarction(MI). Design: Case-control study. Setting: 36 hospitals in a 5-county area. Participants: 1718 case-pa-tients with a first, nonfatal MI admitted to these hospitals and 6800 controls randomly selected from the same counties. Measurements: Self-reported medication use assessed through telephone interviews. Results: The adjusted odds ratio for MI among celecoxib users, relative to persons who did not use nonaspirin nonsteroidal anti-inflammatory drugs(NSAIDs), was 0.43(95%CI, 0.23 to 0.79) compared with 1.16(CI, 0.70 to 1.93) among rofecoxib users. The use of rofecoxib was associated with a statistically significant higher odds of MI compared with the use of celecoxib(adjusted odds ratio for rofecoxib vs. celecoxib, 2.72[CI, 1.24 to 5.95]; P=0.01). Nonselective NSAIDs were associated with a reduced odds of nonfatal MI relative to nonusers. Comparisons of COX-2 inhibitors with nonselective NSAIDs were the following: rofecoxib versus naproxen(odds ratio,3.39[CI, 1.37 to 8.40]) and celecoxib versus ibuprofen or diclofenac(odds ratio, 0.77[CI, 0.40 to 1.48]). Limitations: The possibility of recall bias and uncontrolled confounding in this observational study limit the ability to make definitive conclusions. The association of celecoxib with a lower odds of MI could have occurred by chance. Only about 50%of eligible participants completed telephone interviews. Conclusion: Celecoxib and rofecoxib were associated with different odds of MI. Cardiovascular effects among the COX-2 inhibitors seem different, but further studies, preferably randomized trials, are needed to fully understand the spectrum of effects of COX-2 inhibitors and potential differences among them. Background: Studies have postulated that cyclooxygenase-2 (COX-2) selective inhibitors affect cardiovascular risk through various mechanisms. Some of these mechanisms could increase risk (for example, inhibition of prostacyclin production), and some could decrease risk (for example, inhibition Objective: To determine the effect of COX-2 inhibitors on risk for nonfatal myocardial infarction (MI). Design: Case-control study. Setting: 36 hospitals in a 5-county area. Participants: 1718 case-pa- tients with a first, nonfatal MI admitted to these hospitals and 6800 controls randomly selected from the same counties. Results: The adjusted odds ratio for MI among celecoxib users, relative to persons who did not use nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs), was 0.43 (95% CI, 0.23 to 0.79) compared with 1.16 (CI, 0.70 to 1.93) among rofecoxib users. The use of rofecoxib was associated with a statistically significant higher odds of MI compared with the use of celecoxib (adjusted odds ratio for rofecoxib vs. celecoxib, 2.72 [CI, 1.24 to 5.95]; P = 0.01). Nonselective NSAIDs were associated with a reduced odds of nonfatal MI relative to nonusers. Comparisons of COX-2 inhibitors with nonselective NSAIDs were the following: rofecoxib versus naproxen (odds ratio, 3.39 [CI, 1.37 to 8.40]) and celecoxib versus ibuprofen or diclofenac (odds ratio, 0.77 [CI, 0.40 to 1.48]) Limitations: The possibility of recall bias and uncontrolled confounding in this observational study limit the ability to make definitive conclusions. The association of celecoxib with a lower odds of MI could have occurred by chance. Only about 50% of eligible participants completed telephone interviews. Conclusion: Celecoxib and rofecoxib were associated with different odds of MI. Cardiovascular effects among the COX-2 inhibitors seem different, but further studies, preferably randomized trials, are needed to fully understand the spectrum of effects of COX-2 inhibitors and potential differences among them.