The aim of this observational, prospective, nonrandomized study was to assess long-term psychometric outcomes of surgical treatment of HIV-related facial lipoatrophy. Two hundred ninety-nine participants (70.8% male) consecutively attending the Metabolic Clinic of Modena and Reggio Emilia University from November 2005 to July 2006, undergoing surgical interventions for HIV-related facial lipoatrophy were enrolled. Fifty-four (18.1%) underwent facial lipofilling, which consists of the harvesting of a small, intact parcel of fatty tissue with processing that removes the nonviable components and of the transport of fatty parcels through a small cannula to implant the graft in a manner that provides nutrition and anchors the fat to the host tissue. After an initial lipofilling, 24 (8%) needed polylactic acid injections to correct cheek asymmetry, 91 (30.4%) received only polylactic acid infiltrations, and 130 (43.5%) polyacrylamide infiltrations only. Subjective outcome measures were face aesthetic satisfaction, body image perception, depression evaluated by a visual analogue scale (VAS), the Assessment of Body Change and Distress questionnaire (ABCD), and by the Beck Depression Inventory questionnaire, respectively. Objective measure was cheek thickness evaluated by a 7.5-MHz frequency ultrasound probe perpendicular to the skin surface at the nasolabial fold, the corner of the mouth, the zygomatic arch, and centrally between these points in the buccal fat pad area. Both subjective and objective variables were evaluated at baseline and 48 weeks after end of surgical treatment. All 299 participants had significant improvement of the aesthetic satisfaction for the face (VAS from 2.9 +/- 2.1 to 6.2 +/- 2.1, p < 0.0001), of body image satisfaction (ABCD question 7 from 3.8 +/- 1 to 3.1 +/- 1 p < 0.0001 and ABCD question 8 from 70.7 +/- 16.7 to 77.2 +/- 17.2 p < 0.0001), of depression score (Beck score from 11.4 +/- 8.3 to 9.4 +/- 7.8 p = 0.001). Participants experienced a significant augmentation of both cheeks' thickness (right cheek from 4.3 +/- 1.9 mm to 9.5 +/- 3 mm p < 0.0001, left cheek from 4.4 +/- 2 mm to 9.6 +/- 3.1 mm, p < 0.0001). Our data suggest that facial surgery is an important option in the treatment of HIV-related lipoatrophy as an integral part of the management of HIV infection, because of the important and lasting psychological benefits.