BACKGROUND: The first long-acting injectable antiretroviral, cabotegravir/rilpivirine (LA-CAB/RPV), was approved by the Food and Drug Administration (FDA) in January 2021 for persons with human immunodeficiency virus (HIV) suppressed on their current regimen. Body mass index (BMI) ≥30 kg/m2 has been identified as a risk factor for virologic failure; however, data are limited due to small sample sizes. The aim of this study was to evaluate the impact of BMI on the efficacy of LA-CAB/RPV in a real-world setting. METHODS: A retrospective, multicenter cohort study was conducted from 22 January 2021 to 15 February 2023 in individuals who received LA-CAB/RPV every 4 (Q4w) or 8 weeks (Q8w). Individuals included were virologically suppressed on their current regimen, received at least 1 dose of LA-CAB/RPV, and had a follow-up viral load post initiation. RESULTS: A total of 374 individuals across 5 centers were included, with a BMI ≥30 kg/m2 in 148 (39.5%) individuals. Most individuals received a Q8w (68%) regimen, and the incidence of viral load ≥50 copies/mL was similar between those with BMI ≥30 kg/m2 (12%) as compared to those with BMI <30 kg/m2 (9%) (incidence rate ratio [IRR] 1.31; 95% confidence interval [CI]: .69-2.46, P = .4). Confirmed virologic failure occurred in 0.8% of individuals overall, with 2 of the 3 cases occurring in those with BMI ≥30 kg/m2. CONCLUSIONS: The data from this real-world cohort demonstrates no difference in virologic outcomes for individuals with BMI ≥30 kg/m2 as compared to those with BMI <30 kg/m2 suggesting that higher BMI alone should not preclude use of LA-CAB/RPV in eligible individuals.