OBJECTIVE: Home-based exercise is an alternative exercise mode to a structured supervised program to improve symptoms in patients with peripheral artery disease (PAD), but little is known about whether the slow-paced and less intense home program also elicits changes in vascular and inflammatory biomarkers. In an exploratory analysis from a randomized controlled trial, we compared changes in vascular and inflammatory biomarkers in patients with symptomatic PAD (typical and atypical of claudication) after home-based exercise and supervised exercise programs and in an attention-control group. METHODS: A total of 114 patients were randomized into one of the three groups (n = 38 per group). Two groups performed exercise interventions, consisting of home-based and supervised programs of intermittent walking to mild to moderate claudication pain for 12 weeks; a third group performed light resistance training as a nonwalking attention-control group. Before and after intervention, patients were characterized on treadmill performance and endothelial effects of circulating factors present in sera by a cell culture-based bioassay on primary human arterial endothelial cells, and they were further evaluated on circulating vascular and inflammatory biomarkers. RESULTS: Treadmill peak walking time increased (P = .008) in the two exercise groups but not in the control group (P > .05). Cultured endothelial cell apoptosis decreased after home-based exercise (P < .001) and supervised exercise (P = .007), and the change in the exercise groups combined was different from that in the control group (P = .005). For circulating biomarkers, increases were found in hydroxyl radical antioxidant capacity (P = .003) and vascular endothelial growth factor A (P = .037), and decreases were observed in E-selectin (P = .007) and blood glucose concentration (P = .012) after home-based exercise only. The changes in hydroxyl radical antioxidant capacity (P = .005), vascular endothelial growth factor A (P = .008), and E-selectin (P = .034) in the exercise groups combined were different from those in the control group. CONCLUSIONS: This exploratory analysis found that both home-based and supervised exercise programs are efficacious to decrease cultured endothelial cell apoptosis in patients with symptomatic PAD. Furthermore, a monitored home-based exercise program elicits additional vascular benefits by improving circulating markers of endogenous antioxidant capacity, angiogenesis, endothelium-derived inflammation, and blood glucose concentration in patients with symptomatic PAD. The novel clinical significance is that important trends were found in this exploratory analysis that a contemporary home-based exercise program and a traditional supervised exercise program may favorably improve vascular and inflammatory biomarkers in addition to the well-described ambulatory improvements in symptomatic patients with PAD.