Background: Prior studies found overweight or obese HIV-infected individuals had greater early CD4+ cell recovery on antiretroviral therapy (ART), but the results have been inconsistent. We assessed the longitudinal relationship between body mass index (BMI) and CD4+ cell recovery on ART in a large, multisite cohort to identify potential physiologic links between adiposity and CD4+ cell expansion. Methods: We modeled the relationship of time-updated BMI with CD4+ count in patients starting ART from 17 North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) cohorts. The primary analysis used a linear mixed effects model incorporating up to 13 years of data per patient and adjusted for age, sex, race, ART regimen, baseline CD4+ count and other covariates. Sensitivity analyses limited the cohort to patients with sustained viral suppression or censored at virologic failure. Results: Fourteen thousand eighty-four HIV-infected individuals initiating ART contributed data between 1998 and 2010. Timeupdated BMI was significantly associated with CD4+ cell recovery over time (P < 0.001). After 5 years of ART, the mean CD4+ count at a BMI of 30 kg/m2 was 22% higher than at a BMI of 22 kg/m2 (606 vs. 498 cells per microliter) and 34% higher at a BMI of 40 kg/m2 (665 vs. 498 cells per microliter). Results were similar in the sensitivity analyses. Discussion: Higher BMI is associated with long-term advantages in immune recovery on ART. Although it is unclear if this impacts health outcomes, including balancing the negative health effects of obesity, elucidating the underlying mechanism could identify therapies for patients with suboptimal immune reconstitution.