Objective: To describe national annual rates of nonoccupational postexposure prophylaxis (nPEP) in the United States. Design: Retrospective cohort study of commercially insured individuals in the Merative MarketScan Database from January 1, 2010 to December 31, 2019. Methods: Patients at least 13 years old prescribed nPEP per recommended Centers for Disease Control and Prevention guidelines were identified using pharmacy claims. Rates of use were described overall and stratified by sex, age group, and region. These rates were qualitatively compared to the diagnosis rates of human immunodeficiency virus (HIV) observed in the data. Joinpoint analysis identified inflection points of nPEP use. Results: Eleven thousand, three hundred and ninety-seven nPEP users were identified, with a mean age of 33.7 years. Most were males (64.6%) and lived in the south (33.2%) and northeast (32.4%). The rate of nPEP use increased 515%, from 1.42 nPEP users per 100 000 enrollees in 2010 to 8.71 nPEP users per 10 000 enrollees in 2019. The comparative nPEP use rates among subgroups largely mirrored their HIV diagnosis rates, that is, subgroups with a higher HIV rate had higher nPEP use. In the Joinpoint analysis significant growth was observed from 2012 to 2015 [estimated annual percentage change (EAPC): 45.8%; 95% confidence interval (CI): 29.4 – 64.3] followed by a more moderate increase from 2015 to 2019 (EAPC 16.0%; 95% CI: 12.6–19.6). Conclusions: nPEP use increased from 2010 to 2019, but not equally across all risk groups. Further policy interventions should be developed to reduce barriers and ensure adequate access to this important HIV prevention tool.