This study examined years of potential life lost (YPLL) before age 65 years to assess the relative impact of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) versus other leading causes of death on premature mortality in New York City, New York, between 1983 and 1994. Most causes of death showed substantial year-to-year variation in YPLL, with the exception of HIV/AIDS. The YPLL attributed to HIV/AIDS increased monotonically from 11,866 in 1983 to 167,317 in 1994, a nearly 15-fold increase. The rank order of the relative contribution of HIV/AIDS to total YPLL changed from the eighth leading cause of death to the leading cause. YPLL from heart disease, which ranked second in 1983, declined to fourth in 1994, homicide was unchanged, and chronic liver disease declined from fifth to ninth rank. The annual YPLL attributed to malignant neoplasms was similar to that for heart disease, but peaked in 1984, and the reduction over the subsequent decade was about 13%. Total YPLL was 78% greater among males than among females in 1983 and was nearly twice as high in 1994. Premature mortality decreased steadily for non-Hispanic whites, from 150,967 to 135,027 years for the years 1983–1994, while increasing 20% among blacks (from 179,176 to 215,826 years) and 48% among Hispanics (from 89,869 to 132,869 years). Among blacks and Hispanics, homicide contributed more years of YPLL than did either heart disease or malignant neoplasms in every year of observation. The HIV/AIDS epidemic and mortality associated with violence have become important public health challenges to the health and well-being of New Yorkers. Am J Epidemiol 1998;147:840–5.