Onset of acute myocardial infarction (AMI) follows a diurnal periodicity, with a peak incidence between 6:00 a.m. and noon. Beta blockers and aspirin decrease the rate of AMI and blunt the peak incidence, but such an effect has not been evaluated for angiotensin-converting enzyme inhibitors. The effect of ramipril on onset of symptomatic AMI was evaluated in 4-hour periods over a 24-hour cycle in men and women who were > or =55 years of age, had cardiovascular disease or diabetes mellitus with > or =1 other risk factor, and participated in the Heart Outcomes Prevention Evaluation (HOPE) trial. During the 4.5-year follow-up, AMI was documented in 383 of 4,596 participants allocated to ramipril and in 491 of 4,598 participants allocated to placebo (8.3% vs 10.7%, p <0.001). Ramipril decreased rates of AMI at each period and attenuated, but did not blunt, the peak incidence. In conclusion, inhibiting angiotensin-converting enzyme decreased AMI over a 24-hour period, but this enzyme does not seem to play a major role in the circadian periodicity of this acute event.