We hypothesized that measures of arterial stiffness and wave reflection influence functional capacity of patients with peripheral arterial disease (PAD). Consecutive patients (n=106, 69+/-10 years, 66% men) referred for lower extremity arterial evaluation were studied. Radial artery pulse waveforms were obtained by applanation tonometry and an ascending aortic pressure waveform derived by a transfer function. Aortic augmentation index (AIx) is the difference between the first and second systolic peak of the ascending aortic pressure waveform indexed to the pulse pressure (PP) and T(r) is the reflected wave arrival time. Ankle-brachial index (ABI) and walking distance were measured as per laboratory protocol after excluding patients with non-compressible vessels (ABI>1.5) and severe PAD (ABI<0.5). To account for right-censoring of walking distances in patients completing the 5 min walk (n=56), we used survival analysis to identify variables associated with walking distance. Mean (+/-S.D.) values were: AIx, 31.2+/-10.9%; T(r), 134+/-18 ms; PP, 66.5+/-17.1 mmHg; ABI, 0.87+/-0.22; walking distance, 177+/-75 m. In both multivariable accelerated failure time (AFT) and Cox proportional-hazards models, older age, female sex, greater body mass index, lower ABI, and a measure of arterial stiffness (higher AIx and PP, lower T(r)) were associated with a lower walking distance. Higher AIx and lower T(r) were associated with a lower walking distance even after adjustment for PP as well as in the subset of patients with PAD (ABI<0.9 at rest or post-exercise, n=82). In conclusion, measures of arterial stiffness and wave reflection are associated with walking distance in patients with PAD and may be a target of therapy in such patients.