Background. Vitamin D insufficiency is prevalent in human immunodeficiency virus-positive (HIV+) persons. Human immunodeficiency virus and antiretroviral therapy (ART) may create unique risk factors, and the optimal vitamin D repletion and maintenance regimen in HIV+ persons remains unclear. Methods. Human immunodeficiency virus-positive adults on suppressive ART underwent routine serum 25-hydroxyvitamin D (25OHD) screening. Persons with vitamin D insufficiency (25OHD <30 ng/mL) received open-label, oral vitamin D3 50 000 international units (IU) twice weekly for 5 weeks, then 2000 IU daily to complete 12 weeks. We predicted 70% (95% confidence interval, 60%-80%) repletion to 25OHD ≥30 ng/mL compared with 85% among historical HIV-negative controls. Eighty participants provided 91% power to detect this difference. Ability to maintain 25OHD ≥30 ng/mL after 24 weeks was also assessed. Results. Baseline characteristics were similar between the 82 vitamin D insufficient and 40 sufficient persons enrolled: 95% male, 60% white, 88% nonsmokers, median age 49 years, body mass index 26 kg/m(2), and CD4(+) T lymphocyte count 520 cells/mm(3). After 12 weeks, 81% (66 of 82) of insufficient persons achieved 25OHD ≥30 ng/mL (P = .32 vs historical controls), with only older age (odds ratio [OR] = 1.06; P = .06), higher baseline 25OHD (OR = 1.14; P < .01), white race (OR = 3.39; P = .04), and current smoking (OR = 0.25; P = .06) associated with successful repletion. After 24 weeks, 73% (48 of 66) maintained 25OHD ≥30 ng/mL, with tenofovir (OR = 5.00; P = .01) and abacavir use (OR = 0.23; P = .02) associated with success and failure, respectively, to maintain 25OHD levels. Conclusions. The 25OHD repletion rates were comparable between HIV+ adults on suppressive ART and historical HIV-negative controls, indicating that successful oral repletion can be achieved in this population.