Poly-L-lactic acid, a synthetic biodegradable polymer, is available as an injectable intradermal implant for use in the correction and restoration of the signs of facial lipoatrophy in patients with HIV infection. In a 96-week noncomparative study in HIV-infected patients with severe facial lipoatrophy, 41% of patients treated with intradermal poly-L-lactic acid injections had a total cutaneous thickness of >10 mm at the nasogenian fold at week 24. Poly-L-lactic acid was injected into multiple sites of each cheek at baseline and at weeks 2, 4, and 6. Significant (p < 0.001) increases from baseline in total cutaneous thickness were reported at all evaluation time points up to 96 weeks after the start of treatment. In a randomized, nonblind study, significant (p < 0.001) increases from baseline in dermal thickness were observed at week 24 in HIV-infected patients with facial lipoatrophy who received immediate or deferred (by 12 weeks) treatment with poly-L-lactic acid, administered by injection into multiple intradermal sites every 2 weeks (three injection sessions in total). Improvements in depression and anxiety scores, patient visual analog scale assessments, and photographic assessments were also reported in patients treated with poly-L-lactic acid in the immediate versus deferred treatment trial. Poly-L-lactic acid was generally well tolerated. No serious adverse events were reported.