This prospective study explored effectiveness and safety of Macrolane VRF30 for treatment of buttock lipoatrophy in HIV-infected subjects. Ten subjects who were unable to sit for more than 30 minutes because of pain were injected with a mean of 276 mL and followed for 18 months. The pain score was reduced, and the time that subjects could sit was increased at least up to 9 months post treatment. There was no local displacement of gel. Five mild adverse events occurred; all related to the injection procedure. This pilot study indicates that Macrolane treatment of buttock lipoatrophy is a promising, well-tolerated method that reduces pain at sitting and improves buttock appearance.