Medication nonadherence diminishes the benefits of preexposure prophylaxis (PrEP) for the 1.2 million Americans at risk for HIV exposure. To describe HIV PrEP treatment patterns among Medicare Advantage Prescription Drug (MAPD) plan and commercially insured beneficiaries. This retrospective cohort study identified patients aged 16 to 89 years with at least 1 dispensing of emtricitabine-tenofovir disoproxil fumarate from July 2012, through December 2020, or emtricitabine-tenofovir alafenamide from October 2019 through December 2020, and who were continuously enrolled at least 12 months prior to and following the earliest PrEP claim. Outcomes were HIV PrEP adherence measured by proportion of days covered (PDC) using 2 binary thresholds of 0.60 (4 doses/week) and 0.80 (5-6 doses/week) and duration of index treatment episode, total time on treatment, and total number of prescription fills. The study cohort of 707 (292 MAPD plan, 415 commercial) was predominantly made up of male patients (90.0%) and resided in the South (78.9%) with a mean age of 46.2 years (MAPD plan: 54.5, commercial: 40.4). Both populations engaged in high-risk sexual behavior (All: 18.7%, MAPD plan: 16.8%, commercial: 20.0%) and experienced sexually transmitted infections (All: 3.3%, MAPD plan: 2.1%, commercial: 4.1%). The mean index treatment episode length was 297.0 days (MAPD plan: 283.6, commercial: 306.5). Total time on treatment was 477.3 days (MAPD plan: 450.7, commercial 496.0). At 3 months, 84.9% (MAPD plan: 83.6%, commercial: 85.8%) and at 12 months, 58.7% (MAPD plan: 57.2, commercial: 59.8) of patients achieved a PDC of at least 0.80. At 3 months, 100.0% (MAPD plan: 100.0%, commercial: 100.0%), and at 12 months, 74.3% (MAPD plan: 70.2%, commercial: 76.9%) of patients achieved a PDC of at least 0.60. The cohort had a mean of 16.4 fills of 30 days (MAPD plan: 16.4, commercial: 16.3) supply. There is an opportunity for clinical programs to focus on improving longer-term PrEP adherence among individuals at risk for HIV exposure.