Objective: To identify risk factors for the development of lipodystrophy in HIV infected patients on highly active antiretroviral therapy. Methods: A survey among patients with HIV infection using an anonymous questionnaire was conducted in 10 European countries between December 1998 and December 1999. Nine hundred and four people receiving antiretrovirals, were included in the analyses. Results: 368 (41%) people reported an increase in abdominal girth since commencing current antiretroviral treatment. Breast enlargement was reported by 106 people (12%). Lipoatrophy signs were reported by approximately one-third of the people: 291 (32%) complained about decrease in facial fat and 300 (33%) reported decrease in buttock fat. One hundred and thirty-one (15%) people reported both lipoatrophy signs and an increase in abdominal girth (mixed lipodystrophy syndrome). In multivariate analysis, the development of the mixed lipodystrophy syndrome was associated with a longer use of indinavir (OR=1.03, 95% CI: 1.00–1.06), ritonavir (OR=1.06, 1.02–1.09) and stavudine (OR=1.05, 1.02–1.08) and also with age, a longer duration of HIV seropositivity and an advanced stage of HIV infection. Conclusions: This study suggests that multiple factors are associated with the occurrence of lipodystrophy, including the prolonged use of protease inhibitors.