Topical hyaluronic acid (HA) is routinely used in the local treatment of chronic wounds, but few data have been reported to date. A 60-day double-blind, randomised, controlled superiority trial was designed to investigate the efficacy and safety of a gauze pad containing HA in local treatment of venous leg ulcers, compared with its neutral vehicle. The primary endpoint was the percentage of wound size reduction after 45 days. Totally 89 patients were included. At day 45, the percentage of ulcer surface reduction was significantly greater in the HA group (73 ± 4*6%) versus neutral vehicle group (46 ± 9*6%) (P = 0*011). The number of healed ulcers was significantly higher in the HA group at day 45 (31*1% versus 9*3% respectively) and day 60 (37*8% versus 16*3% respectively; P < 0*05). At day 30, pain intensity based on visual analogue scale was significantly lower in the HA group (12*4 mm ± 2*6 versus 22*8 mm ± 3*8; P = 0*026). Tolerance of both treatments was comparable in the two groups. HA gauze pad, in local treatment of venous leg ulcers, was significantly more effective than the neutral vehicle on wound size reduction, healed ulcers rate and pain management with a good safety profile.