Background It is currently unknown whether 6 months of supervised treadmill exercise has a durable benefit on 6-minute walk performance, even after exercise is completed, in people with peripheral artery disease. Methods and Results A total of 156 participants with peripheral artery disease were randomized to 1 of 3 groups: supervised treadmill exercise, supervised resistance training, or attention control. Participants received supervised sessions during months 1 to 6 and telephone contact during months 6 to 12. Primary outcomes were change in 6-minute walk distance and short physical performance battery at 6-month follow-up and have been reported previously. Secondary outcomes were change in 6-minute walk and short physical performance battery at 12-month follow-up and are reported here. A group of 134 participants (86%) completed the 12-month follow-up. At 6-month follow-up, compared with control, 6-minute walk distance improved in the treadmill exercise group (+36.1 m, 95% CI =13.9-58.3, P=0.001). Between 6- and 12-month follow-up, 6-minute walk distance significantly declined (-28.6 m, 95% CI=-52.6 to -4.5, P=0.020) and physical activity declined -272 activity units (95% CI =-546 to +2, P=0.052) in the treadmill exercise group compared with controls. At 12-month follow-up, 6 months after completing supervised treadmill exercise, change in 6-minute walk distance was not different between the treadmill exercise and control groups (+7.5, 95% CI =-17.5 to +32.6, P=0.56). There were no differences in short physical performance battery change between either exercise group and control at 6-month or 12-month follow-up. Conclusions A 6-month supervised treadmill exercise intervention that improved 6-minute walk distance at 6-month follow-up did not have persistent benefit at 12-month follow-up. These results do not support a durable benefit of supervised treadmill exercise in peripheral artery disease. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Identifier: NCT 00106327.