In a placebo-controlled trial skeletal muscle biopsies were taken proximal and distal to the site of arterial stenosis, before cross-clamp and 20 min following reperfusion, in 8 well-matched critical limb ischaemia patients undergoing femorodistal bypass. Capillary endothelial swelling – a sign of reperfusion injury – was assessed following infusion with iloprost, a prostacyclin analogue, the prolonged beneficial effect of which on vascular graft flow rates has been demonstrated previously. Electron microscopy and image analysis of calf capillaries confirmed that critical limb ischemia patients had endothelial cell swelling before bypass, and that cross-clamp ischaemia caused further endothelial swelling in the placebo group. Samples from muscles proximal to the site of the bypass showed similar changes, indicating that systemic capillary damage occurs in muscle remote from the area of ischaemia. Iloprost treatment prevented endothelial swelling and increased the mean capillary lumen cross-sectional area. Iloprost, therefore, has a potentially beneficial effect on capillary function by limiting reperfusion injury during femorodistal bypass.