OBJECTIVES To assess the effect of pain-free treadmill training on red blood cell deformability and walking distance in patients with claudication. DESIGN Randomized-controlled trial of exercise training. SETTING Patients were recruited from the primary care, vascular outpatient clinic. PATIENTS A total of 60 patients with peripheral arterial occlusive disease (stage II according to Leriche-Fontaine) were randomized into the treadmill program or a control group. Fifty-five patients completed the study (27 in the exercising group and 28 in the control group). INTERVENTIONS Patients in the exercising group were walking on the treadmill 3 times a week for 3 months. Each session consisted of 1 hour repetitive walking [performed to 85% of the pain-free walking time (PFWT)] was supervised by a qualified physiotherapist. MAIN OUTCOME MEASUREMENTS Changes in erythrocyte deformability and treadmill walking performance (PFWT, maximal walking time) were assessed in both groups before the study and after 3 months. RESULTS After 3 months of treadmill training, red blood cell deformability in the exercising group significantly increased (P<0.01). No significant changes were seen in the erythrocyte deformability in the control group. PFWT was prolonged by 102% from 191+/-34 to 386+/-60 seconds (P<0.01), and maximal walking time increased by 49% from 438+/-62 to 656+/-79 seconds (P<0.01) in the exercising group, whereas these changes were insignificant in the control group. CONCLUSIONS A significant improvement of walking ability over 3 months of pain-free treadmill training is associated with a significant increase in red cell deformability in patients with claudication.