The increased life expectancy among HIV-infected persons treated with combination antiretroviral therapy (ART), risk behaviors, and co-morbidities associated with ART place HIV-infected persons at risk for non-HIV-related causes of death. We used the San Francisco HIV/AIDS registry to identify deaths that occurred from January 1996 through December 2011. Temporal trends in AIDS- and non-AIDS-related mortality rates, the proportion of underlying and contributory causes of death, and the ratio of observed deaths in the study population to expected number of deaths among California men aged 20-79 (standardized mortality ratio [SMR]) of underlying causes of death were examined. A total of 5338 deaths were identified. The annual AIDS-related death rate (per 100 deaths) declined from 10.8 in 1996 to 0.9 in 2011 (p<0.0001), while the annual death rate from non-AIDS-related causes declined from 2.1 in 1996 to 0.9 in 2011 (p<0.0001). The proportion of deaths due to all types of heart disease combined, all non-AIDS cancers combined, mental disorders resulting from substance abuse, drug overdose, suicide and chronic obstructive pulmonary disease increased significantly over time. The SMRs for liver diseased decreased significantly over time but remained elevated. Our data highlight the importance of age-related causes of death as well as deaths from causes that are, at least in part, preventable.