OBJECTIVE To evaluate the safety and effectiveness of soft tissue augmentation with calcium hydroxylapatite (CaHA) microspheres in an aqueous gel in patients with facial lipoatrophy (FLA) secondary to human immunodeficiency virus (HIV) disease. METHODS This 12-month open-label, prospective study enrolled 30 subjects (29 men and 1 woman) with HIV-associated FLA. After the initial treatment phase (up to 2 injections, 30 days apart), patients were followed up at 3, 6, and 12 months. Patients were offered touch-up injections at 6 and 12 months. Measurements included confirmed changes in the Global Aesthetic Improvement Scale and in cheek thickness. RESULTS Average initial treatment volume was 9.5 mL per patient (both sides); total volumes per patient after 12 months averaged 16.1 mL. At all time points, all patients were rated as improved or better and responded affirmatively to satisfaction questions. Cheek thickness measurements increased substantially over baseline (p<.001). Most commonly reported adverse events were edema (93%), ecchymosis (83%), and erythema (77%). CONCLUSIONS CaHA is an appropriate and well-tolerated treatment for patients with HIV-associated FLA. With an excellent safety profile, CaHA provides immediate correction of FLA and appears to provide lasting improvement in appearance. BioForm Medical provided, in part, Radiesse soft tissue filler and an unrestricted educational grant for this study. Both physicians are members of the BioForm Clinical Advisory Board.