This purpose of this study was to evaluate the effect of aprotinin, a serine protease inhibitor, in ischaemia- and reperfusion-injured myocutaneous flaps and skin flaps. Flap survival, microcirculatory platelet accumulation, and regional blood flow were investigated in seventeen pigs which had been subjected to 8 h of ischaemia and 18 h of reperfusion. The pigs were randomly assigned to aprotinin treatment (n = 9) or saline (n = 8). In-vitro studies were performed to investigate the influence of aprotinin on the activated partial thromboplastin time. The survival of skeletal muscle correlated positively with the concentration of aprotinin (P = 0.02) and could not be explained by regional changes in blood flow. Platelet accumulation was decreased in aprotinin-treated muscle (P = 0.04). In-vitro (n = 10), 100 kallikrein inactivator units/ml aprotinin prolonged the activated partial thromboplastin time both in plasma (P = 0.001) and in blood (P = 0.002), suggesting an anticoagulant rather than a procoagulant effect. In conclusion, aprotinin at high concentrations may be beneficial for the survival of skeletal muscle and provides protection from platelet accumulation in the microcirculation of skeletal muscle exposed to ischaemia and reperfusion injury.