The efficacy and safety of pentoxifylline (400 mg tid orally) and acenocoumarol, administered singly or in combination, in the treatment of intermittent claudication associated with chronic occlusive arterial disease were evaluated in a multi-center, randomized, factorial, blind clinical trial involving 146 patients. The response to treatment was assessed by measuring pain-free walking time on the treadmill and by Doppler ankle/arm systolic pressure ratio at rest and after treadmill. Both pentoxifylline and acenocoumarol were significantly more effective than placebo in increasing the proportion of patients who improved their performance on the treadmill after one year of treatment. Benefit from active treatment was also apparent from the results of Doppler examinations performed after physical exercise. No significant differences were observed in comparing the effect of one active drug versus the other or versus the combined treatment. Five major hemorrhagic complications were registered in anticoagulated patients, two fatal cerebral hemorrhages and one gastrointestinal bleeding occurring in the group treated with both active drugs. The investigators conclude that (1) pentoxifylline is effective and safe in the treatment of patients with intermittent claudication (2) the benefits of oral anticoagulant therapy are outweighed by the risk of serious bleeding, and (3) the risk of bleeding is probably increased by the combined treatment with pentoxifylline.