Background. The natural history of peripheral atherosclerosis in young adults appears to be unfavorable compared with that in older patients. No universally accepted definition of "premature" atherosclerosis exists, however, making comparison of clinical studies difficult. This study examined age-related differences in distribution of atherosclerotic lesions and determined an age threshold at which such differences became apparent. Such a threshold may provide a definition of premature atherosclerosis. Methods. Arteriograms of all patients 49 years of age and younger undergoing evaluation of lower extremity ischemia during the past 5 years were reviewed and the findings were tabulated. Medical records were reviewed to obtain demographic data, assess risk factors, and confirm disease etiology. Exclusion criteria included normal arteriograms (three patients), history of acute or remote trauma (six patients), unclear cause of ischemic symptoms (three patients), arteritis (four patients), aneurysmal disease (one patient), and acute ischemia without prior chronic symptoms (12 patients). For comparison we also reviewed arteriograms performed during the same period in 140 patients older than 50 years of age who had chronic lower extremity ischemia caused by atherosclerosis. Results. The mean age of the 59 study patients was 43.4±5.8 years (median age, 46 years; range, 25 to 49 years). Arteriograms were available in all cases; medical records were available in 54 (92%). Atherosclerosis involved only the aortoiliac segment in 25 patients (42%), the femoropopliteal-tibial arteries alone in 21 (36%), and both levels in 13 (22%). Patients with distal atherosclerosis had a higher prevalence of diabetes than those with proximal atherosclerosis (p=0.004). Ninety-two (66%) of the 140 patients older than 50 years of age had atherosclerosis confined to a single arterial segment, which was not significantly different from the prevalence of single-level disease in the study group. However, 25 (54%) of the 46 study patients with single-level atherosclerosis had aortoiliac disease compared with only 15 (16%) of 92 patients older than 50 years of age with single-level disease (p<0.001). Conclusions. In contrast to the pattern of disease in older adults, atherosclerosis in young, nondiabetic patients most commonly involves the aortoiliac segment. Differences in lesion distribution become increasingly apparent with age but are most striking between those 49 years of age and younger and those 50 years of age and older. Accordingly, we propose that premature peripheral atherosclerosis be defined as beginning at or before the age of 49 years.