The aim of this prospective study is to assess the efficacy of a high density hyaluronic acid (HA) subcutaneous injection, Ma-crolane® 20, in hand rejuvenation in the short, medium and long term, regarding treatment benefit, patient satisfaction and possible complications. This study was performed between May 2010 and December 2011. Twenty nine patients were enrolled at random, aged from 51 to 74, phototypes II-IV, and were treated with HA for hand rejuvenation. A clinical follow-up was performed at 2 weeks, and 1, 3, 6, 9 and 12th months after. The quantity of HA injected for each hand was 1-2 ml. Complications were recorded at each control. Ecographic exam was carried out at the first control 2 weeks after treatment in order to determine if a second injection was necessary. Patients answered a satisfaction questionnaire at every control. Only 1 patient presented edema and 3 patients suffered slight ecchymosis. Two patients expressed slight pain with injections and 2 patients needed a second injection after the assessment 2 weeks after. Patients´ satisfaction was higher than clinical and photographic assessment. In our opinion, hand rejuvenation has a low rate of complications with these large-sized particles HA, and it has been well tolerated with a high patient satisfaction and outstanding improvement with respect to: wrinkles, dermal and subcutaneous atrophy and decrease of bony, sinewy and venous prominences. The subjective and objective assessment achieved a good result one year later.