A single session of leg heat therapy (HT) has been shown to elicit increases in leg blood flow and reduce blood pressure (BP) and the circulating levels of endothe- lin-1 (ET-1) in patients with symptomatic peripheral artery disease (PAD). We assessed whether 6 wk of supervised leg HT (3 times/ wk) with water-circulating trousers perfused with water at 48?C improved 6-min walk distance in individuals with PAD compared with a sham treatment. Secondary outcomes included the assessment of leg vascular function, BP, quality of life, and serum ET-1 and ni- trite plus nitrate (NOx) levels. Of 32 PAD patients randomized, 30 [age: 68±8 yr; ankle-brachial index (ABI): 0.6±0.1] completed the 3- and 6-wk follow-ups. Participants completed 98.7% of the treat- ment sessions. Compared with the sham treatment, exposure to HT did not improve 6-min walk distance, BP, popliteal artery reactive hyperemia, cutaneous microvascular reactivity, resting ABI, or serum NOx levels. The change from baseline to 6 wk in scores of the phys- ical functioning subscale of the 36-item Short Form Health Survey was significantly higher in the HT group (control ?6.9±10 vs. HT 6.8±15; 95% confidence interval: 2.5–24.3, P = 0.017). Similarly, the change in ET-1 levels after 6 wk was different between groups, with the HT group experiencing a 0.4 pg/mL decrease (95% confi- dence interval: ?0.8–0.0, P = 0.03). These preliminary results indi- cate that leg HT may improve perceived physical function in symptomatic PAD patients. Additional, larger studies are needed to confirm these findings and determine the optimal treatment regimen for symptomatic PAD patients.