BACKGROUND: Understanding advances in the care and treatment of adults with HIV as well as remaining gaps requires comparing differences in mortality between persons entering care for HIV and the general population. OBJECTIVE: To assess the extent to which mortality among persons entering HIV care in the United States is elevated over mortality among matched persons in the general U.S. population and trends in this difference over time. DESIGN: Observational cohort study. SETTING: Thirteen sites from the U.S. North American AIDS Cohort Collaboration on Research and Design. PARTICIPANTS: 82 766 adults entering HIV clinical care between 1999 and 2017 and a subset of the U.S. population matched on calendar time, age, sex, race/ethnicity, and county using U.S. mortality and population data compiled by the National Center for Health Statistics. MEASUREMENTS: Five-year all-cause mortality, estimated using the Kaplan-Meier estimator of the survival function. RESULTS: Overall 5-year mortality among persons entering HIV care was 10.6%, and mortality among the matched U.S. population was 2.9%, for a difference of 7.7 (95% CI, 7.4 to 7.9) percentage points. This difference decreased over time, from 11.1 percentage points among those entering care between 1999 and 2004 to 2.7 percentage points among those entering care between 2011 and 2017. LIMITATION: Matching on available covariates may have failed to account for differences in mortality that were due to sociodemographic factors rather than consequences of HIV infection and other modifiable factors. CONCLUSION: Mortality among persons entering HIV care decreased dramatically between 1999 and 2017, although those entering care remained at modestly higher risk for death in the years after starting care than comparable persons in the general U.S. population. PRIMARY FUNDING SOURCE: National Institutes of Health.