AIMS: To evaluate the association between impaired heart rate variability (HRV) and cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM). METHODS: A total of 655 patients with T2DM who underwent cardiovascular autonomic function testing were consecutively recruited and followed up prospectively. Time- and frequency-domain HRV were assessed for 5鈥痬in by beat-to-beat heart rate recording. We estimated the development of CVD events during a follow-up period. RESULTS: During a median follow-up of 7.8鈥痽ears, 9.6% (n鈥?鈥?9) of patients developed CVD (10.6 per 1000 patient-years). The mean age and diabetes duration were 54.9鈥?/-鈥?.6鈥痽ears and 9.4鈥?/-鈥?.3鈥痽ears, respectively. Patients who had cardiovascular autonomic neuropathy (CAN) had decreased HRV compared with those with normal autonomic function. Multivariable cox hazard regression analysis revealed the lowest 10th percentile of the SD of the normal-to-normal interval (HR 2.62; 95% CI 1.30-5.31), total power (HR 2.81; 95% CI 1.37-5.79), low-frequency power (HR 2.68; 95% CI 1.28-5.59), and high-frequency power (HR 2.24; 95% CI 1.09-4.59) were significant predictors for developing CVD in patients with T2DM. CONCLUSIONS: Time- and frequency-domain measures of HRV independently predicted cardiovascular outcome in patients with T2DM.