A prospective, randomized clinical trial to study the effect of aspirin on late patency of femoral popliteal and tibial bypass grafts is reported. One hundred limbs in 93 patients were randomized to receive daily 650 mgs aspirin postoperatively (ASA, n = 45) or no aspirin (NASA, n = 55). Indication for surgery was limb salvage in 88% and poor runoff (0-1 vessel) was present in 68%. Graft material consisted of autogenous vein (AV) in 63, expanded PTFE in 82 and composite grafts in five limbs. Distal anastomosis was to the popliteal artery in 72 limbs, tibial vessels in 19 and sequential in nine limbs. Patient followup ranged from 1-51 months (mean 12.97). Sixteen (16%) grafts occluded late, eight each in the ASA and NASA groups, (p greater than .05). No significant differences in graft patency existed between ASA and NASA groups in limbs with AV (88.5% vs 92.9%) or PTFE grafts (74% vs 62%) (p greater than .05). A total of 21 (19%) anastomoses occluded. No differences were noted between ASA and NASA limbs, although patency in AV was greater than PTFE (p less than .05). Cumulative patency rates were 84.4% at 12 months, 81.5% at 24 months, 67.3% at 36 months and 52.4% at 48 months (ASA vs NASA, p greater than .05). Therefore, daily administration of 650 mgs of aspirin did not appear to influence late graft patency of femoral popliteal and tibial AV or PTFE bypass grafts at a mean followup period of 12.97 months.