A prospective controlled study of 144 patients with peripheral obstructive arterial disease was undertaken to evaluate the efficacy of acetylsalicylic acid (ASA) treatment (250 mg daily) on the outcome after lower limb arterial surgery which mainly involved endarterectomy. By random enrollment, 2 groups of 72 patients were formed after the surgery. Patients with ASA treatment for 3 months, starting from the seventh postoperative day, were compared with patients who were not treated with ASA. The patients in both groups had similar characteristics as to sex ratio, age, concomitant diseases, preoperative arm-ankle systolic blood pressure index, and type and primary success of the reconstruction. Forty-seven of the ASA-treated and 48 of the untreated patients reported to continue cigarette smoking. Postoperative ASA-treatment protected against local adverse events which occurred in 15 patients (21%) of the ASA-treated group compared with 31 patients (43%) of the untreated group (p less than 0.01). Among heavy smokers (greater than 15 cigarettes/day) the efficacy of antiplatelet treatment was not detectable. These results imply that, in patients with peripheral arterial disease, ASA prevents platelet interaction to endarterectomized and atherosclerotic lower limb arteries thereby affecting the subsequent risk of occlusion; however, heavy cigarette smoking, which is very common among patients with peripheral arterial disease, counteracts the local antithrombotic potency of ASA.