HIV protease inhibitor (PI) therapy may be associated with cardiac and vascular complications. We assessed the effects of PIs on cardiac function and structure. M-mode, cross-sectional, and Doppler echocardiography were performed in 98 consecutive black adults aged 25 to 45 years with HIV infection who were receiving antiretroviral therapy. Forty-five (56.1%) took PIs (mean duration of PI use: 29.6 +/- 12.2 months). No significant differences between the PI and non-PI groups were found in left ventricular (LV) systolic function and cardiac valve regurgitation. Those who took PIs had a significantly higher interventricular septum thickness (1.1 +/- 0.3 vs. 1.0 +/- 0.2 cm; p =.049), LV posterior wall thickness (1.1 +/- 0.2 vs. 1.0 +/- 0.2; p =.027), and lower ratio of early peak velocity (E wave) to late peak velocity (A wave) (E/A ratio) (1.36 +/- 0.30 vs. 1.53 +/- 0.31; p =.023) than did those who did not take PIs. Linear regression analyses indicated that posterior wall thickness, septum thickness, left atrial dimension, LV mass, and E/A ratios were significantly associated with the log-transformed duration of PI therapy. Despite the proven benefits of PIs in patients with HIV infection, this report demonstrates an association between continued PI intake and LV hypertrophy that should be known and taken into consideration in the analysis of cardiac structure and function in patients with HIV infection.