There is continued concern about protease inhibitors (PIs) causing increased risk of coronary heart disease (CHD) in HIV-infected patients. This ongoing observational study examines CHD and myocardial infarction (MI) hospitalization rates among HIV-positive members of the Kaiser Permanente Medical Care Program of Northern California, before and after PI use, and before and after any antiretroviral therapy (ART). Also, CHD and MI hospitalization rates among HIV-infected members are compared with members not known to be HIV-positive. With 4.1 years' median total follow-up, age-adjusted CHD and MI hospitalization rates were not significantly different before versus after PIs (6.2 vs. 6.7 events per 1000 person-years); or before versus after ART (5.7 vs. 6.8). However, comparing HIV-positive and -negative members, the CHD hospitalization rate was significantly higher (6.5 vs. 3.8, p = .003), and the difference in the MI rate also was higher (4.3 vs. 2.9, p = .07). Differences between HIV-positive and -negative members in the CHD risk factors measured were mixed, and the overall clinical significance of these differences is uncertain. Our data suggest that PIs and other antiretroviral therapies do not yet increase CHD or MI hospitalizations among HIV-infected individuals; however, longer follow-up is needed. Other HIV-related mechanisms may be at work, causing increased CHD and MI risk among all HIV-infected persons.