Objective: Cardiovascular events, such as myocardial infarction and stroke, contribute significantly to the prognosis of patients with peripheral artery disease. Therefore cardiovascular risk reduction is a vital element of treatment in patients with intermittent claudication (IC). The cardiovascular risk is largely determined by modifiable risk factors, which can be treated with medical care and lifestyle adjustments, such as increasing physical activity. The objective of this study was to determine the effects of supervised exercise therapy (SET) on modifiable cardiovascular risk factors in IC patients. Methods: This is a systematic review and meta-analysis of prospective studies on the effects of SET on cardiovascular risk factors in symptomatic IC patients. Studies were eligible if they presented baseline and follow-up values for at least one of the following risk factors: blood pressure (systolic or diastolic), heart rate, lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), glucose, glycated hemoglobin, body weight, body mass index, or cigarette smoking. Pooled mean differences between follow-up and baseline were analyzed using a random-effects model. Data were classified into short-term results (6 weeks-3 months) and midterm results (6-12 months). Statistical heterogeneity was presented as I2 and Q statistic. Results: Twenty-seven studies with a total of 808 patients were included in this review. In the short term, SET resulted in significant improvements of systolic blood pressure (decrease of 4 mm Hg; 10 studies; 95% confidence interval [CI], -6.40 to -1.76; I2, 0%) and diastolic blood pressure (decrease of 2 mm Hg; 8 studies; 95% CI, -3.64 to -0.22; I2, 35%). In the midterm, SET contributed to significant lowering of levels of low-density lipoprotein cholesterol (decrease of 0.2 mmol/L; four studies; 95% CI, -0.30 to -0.12; I2, 29%) and total cholesterol (decrease of 0.2 mmol/L, four studies; 95% CI, -0.38 to -0.10; I2, 36%). No significant effects of SET were identified for heart rate, triglycerides, high-density lipoprotein cholesterol, glucose, glycated hemoglobin, body weight, body mass index, or cigarette smoking. Conclusions: This systematic review and meta-analysis shows favorable effects of SET on modifiable cardiovascular risk factors, specifically blood pressure and cholesterol levels. Despite the moderate quality, small trial sample sizes, and study heterogeneity, these findings support the prescription of SET programs not only to increase walking distances but also for risk factor modification. Future studies should address the potential effectiveness of SET to promote a healthier lifestyle and to improve cardiovascular outcomes in patients with claudication.