Cardiovascular risk is increased in HIV infected patients. We assessed progression of coronary artery calcium (CAC) in patients with HIV infection to identify factors that may help explain progression of atherosclerosis. Prospective, observational study of 132 HIV-infected men receiving chronic antiretroviral therapy (ART); we measured traditional atherosclerosis risk factors and assessed progression of CAC on sequential 64-slice CT scans at an average interval of 11 months (range 6-36). CAC score progression was defined as absolute and percentage change from baseline. During follow-up 45 patients (34%) showed absolute progression of CAC and 34 of them showed >15% yearly progression, a threshold previously associated with a high risk of myocardial infarction. Age, LDL cholesterol, visceral abdominal fat and current T-helper (CD4+) cell count were significantly associated with absolute CAC progression. Progression of subclinical atherosclerosis in HIV patients is associated with traditional coronary risk factors as well as HIV related factors such as the CD4+ cell count. Therefore, immunologic perturbations secondary to HIV infection may contribute to atherosclerosis progression.