Hyperlipidemia has been seen in patients receiving protease inhibitor-based antiretroviral therapy, prompting concern that such patients are at risk for accelerated coronary artery disease (CAD). To assess the risk of CAD in antiretroviral-treated HIV-infected men, we quantified coronary artery calcium (CAC), a sensitive and established marker of subclinical CAD, using electron beam computed tomography (EBCT) of coronary vessels. Sixty HIV-infected men who met the following criteria (cases) were enrolled in the study: age of 40 years or older; naive to antiretroviral therapy or use of a stable antiretroviral regimen for >or=6 months (mean duration, 25.9 months; 41 patients were receiving protease inhibitor therapy); and no known CAD or no use of lipid-lowering agents. EBCT-derived CAC scores, serum lipid levels, history of antiretroviral therapy, and risk factors for CAD were obtained. Each case was compared with three age-, sex-, and race-matched HIV-negative controls randomly selected from a database including >9000 patients who had undergone EBCT. We determined differences in the proportion of cases and controls with CAC scores of >0 (detectable calcium) and clinically significant CAC for age range. There were no statistically significant differences between the number of cases and controls with detectable CAC (33% and 39%, respectively) and clinically significant CAC (18% and 17%, respectively). This study suggests that the rate of coronary atherosclerosis among HIV-infected patients who receive short-term antiretroviral therapy with or without protease inhibitors is not higher than that among age-, sex-, and race-matched HIV-negative controls. These results need to be confirmed in larger long-term studies, with controls well matched for coronary risk factors.