With widespread availability and the use of antiretroviral therapy, patients with human immunodeficiency virus (HIV) in the United States are living long enough to experience non-AIDS–defining illnesses. HIV is associated with an increased risk for cardiovascular disease (CVD) because of traditional CVD risk factors, residual virally mediated inflammation despite HIV treatment, and side effects of antiretroviral therapy. No United States population-wide studies have evaluated patterns of CVD mortality for HIV-infected subjects. Our central hypothesis was that the proportionate mortality from CVD (CVD mortality/total mortality) in the HIV-infected population increased from 1999 to 2013. We used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research online database of the United States public health data to assess proportionate CVD mortality from 1999 to 2013 in the HIV-infected, general, and inflammatory polyarthropathy populations; the inflammatory polyarthropathy population was included as a positive control group. Total mortality in the HIV-infected population decreased from 15,739 in 1999 to 8,660 in 2013; however, CVD mortality increased from 307 to 400 during the same period. Thus, proportionate CVD mortality for the HIV-infected population increased significantly from 1999 to 2013 (p <0.0001); this pattern was consistent across races, particularly for men. In contrast, proportionate CVD mortality decreased for the general and inflammatory polyarthropathy populations from 1999 to 2013. In conclusion, CVD has become an increasingly common cause of death in HIV-infected subjects since 1999; understanding evolving mortality risks in the HIV-infected population is essential to inform routine clinical care of HIV-infected subjects as well as CVD prevention and treatment.