OBJECTIVE: To evaluate the association between a family history of cardiovascular and metabolic diseases or risk factors and the presence of peripheral artery disease (PAD). METHODS: Participants were recruited within one PAD case-control study (CAVASIC, n = 481) and two population-based studies (KORA-F3, n = 3118; KORA-F4, n = 1325). In the KORA studies, an ankle-brachial-index <0.9 and/or symptomatic claudication was defined as PAD. For myocardial infarction, stroke, diabetes mellitus, hypertension, PAD, and obesity, family risk scores (FamRS) were calculated taking into account the number and age of diseased parents and siblings and regressed on prevalent PAD or ankle-brachial-index. RESULTS: A significant association with PAD was found for family history of myocardial infarction and hypertension in a combined analysis of all studies and for family history of PAD in the case-control study. A combined family history score was derived from FamRS myocardial infarction, stroke, diabetes mellitus, hypertension and PAD. A positive family history of at least two and/or a strong positive family history of at least one of these diseases was found to be associated with increased risk of prevalent PAD in all three studies, even after adjustment for classical risk factors (OR = 1.93, 95%CI = [1.53-2.44], p = 2.6 × 10(-8)). CONCLUSION: The presence of a positive family history for cardiovascular and metabolic diseases or risk factors was shown to be associated with the presence of PAD. A FamRS calculation tool that considers age and family size can guide a physician to perform extended examinations to prevent complications and progression of PAD.