BACKGROUND: Hyaluronic acid is a common component of the extracellular matrix, has many medical applications, and is widely used as a soft tissue filler in patients who simultaneously or eventually undergo cosmetic procedures to the areas treated. OBJECTIVE: The objective was to study the effect of hyaluronic acid on wound healing and viability of random-pattern flaps in rats. METHODS AND MATERIALS: Twenty-six male rats were randomly divided into two groups. A cephalically based random dorsal flap was used - 14 rats received hyaluronic acid to the bed of the flap immediately after surgery; 12 served as controls. After 1 week, flap survival was evaluated by fluorescein fluorescence. A t-test statistical analysis of survival relationships was performed. RESULTS: Flap viability in hyaluronic acid-treated rats was slightly better than in controls (average flap length survival 46.7 and 40.6 mm, respectively; p<.2). CONCLUSIONS: Although hyaluronic acid had a slight beneficial effect on flap viability, no significant improvement in flap survival was shown. The lack of any deleterious effect of hyaluronic acid on relatively ischemic tissues is further evidence of its harmless effect during surgical intervention. Further studies should be performed to clarify the potential benefit of hyaluronic acid on random flaps.