BACKGROUND: The objective of this study was to analyze the association between cardiac autonomic modulation and arterial stiffness in patients with peripheral artery disease (PAD). METHODS: This cross-sectional study included one hundred fourteen patients with symptomatic PAD (67.5% men; 65 +/- 7 years; body mass index: 26.8 +/- 4.5 kg/m(2)). Heart rate variability (HRV) was measured within time (standard deviation of all RR intervals [beat to beat heart interval] [SDNN], root mean square of the successive differences between adjacent normal RR intervals [RMSSD], and the proportion of successive RR intervals that differed by more than 50 msec [pNN50]) and frequency (low frequency [LF] and high frequency [HF]) domains. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). Crude and adjusted linear regression analyses examined the relationship between HRV and cfPWV. RESULTS: Nonsignificant crude associations were identified among cfPWV and RMSSD (P = 0.181), SDNN (P = 0.105), pNN50 (P = 0.087), LF (P = 0.376), HF (P = 0.175), and LF/HF ratio (P = 0.426). After adjustments for age, sex, smoking, body mass index, ankle-brachial index, and use of beta-blockers, significant associations were identified among cfPWV and RMSSD (P = 0.037), SDNN (P = 0.049), and pNN50 (P = 0.049). CONCLUSIONS: Cardiac autonomic modulation was significantly associated with arterial stiffness in patients with PAD after adjustment for confounding factors. This relationship may contribute to the enhanced cardiovascular disease risk for PAD patients and provides a target for strategies to improve patient clinical outcomes.