Objective: Peripheral fat loss and visceral fat gain have been reported in HIV infection. There are limited data on long-term change in adipose tissue in HIV-infected patients vs. controls. Therefore, we determined change in regional adipose tissue from baseline examination to 5 years later among participants in the study of Fat Redistribution and Metabolic Change in HIV Infection. Methods: Regional adipose tissue volume was measured using MRI at both examinations in 477 HIV-infected and 214 control men and women. Lipoatrophy was defined as leg subcutaneous adipose tissue (SAT) below the cutoff point marking the lowest decile (10%) of controls at each examination. Results: HIV-infected and control participants showed similar adipose tissue gains. In men, all SAT depots and visceral adipose tissue started lower and remained lower on average in HIV-infected vs. controls. In women, leg and arm SAT also started lower and remained lower in HIV-infected vs. controls. Mean leg SAT of HIV-infected men was 67% of control men at baseline and 65% at follow-up; for women 83% and 77%. At baseline, 48% of HIV-infected participants had lipoatrophy; on average those with baseline lipoatrophy gained 0.96L of leg SAT compared with 1.23L gain for controls in the lowest decile (P = 0.16). At follow-up, 53% of HIV-infected participants had lipoatrophy. In multivariable models, discontinuation of stavudine appeared to produce little gain in leg SAT (∼1.1%/year). Conclusion: HIV-infected participants did not substantially recover SAT compared with controls, although both showed average gains. HIV-associated lipoatrophy persisted after 5 years of follow-up. © 2010 Lippincott Williams & Wilkins.