We aimed this study to test the hypotheses that heart rate (HR) variability, evaluated by ambulatory blood pressure monitoring (ABPM), predicts risk of incident cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM). ABPM was performed in 200 normotensive or hypertensive subjects with T2DM and 257 hypertensive subjects without diabetes (the mean age: 66.9+/-9.2 years; 38% were male). All subjects were untreated at the time of ABPM, and were followed for 67+/-27 months. Various measures of HR variability-standard deviation (s.d.) of HR, the root-mean-square of successive differences (RMSSD) of HR, systolic blood pressure (SBP)-HR relationships evaluated by slope and coefficients of correlation between SBP and HR-were used for the analyses. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals, after controlling for age, sex, body mass index, serum creatinine and 24-h SBP. During follow-up, there were 34 cardiovascular events. Awake HR variability in diabetics was smaller than non-diabetics, but sleep HR variability was similar between the groups. In multivariable analyses, increased sleep HR variability evaluated by s.d. and RMSSD of sleep HR, and slope and correlation coefficient of SBP-HR each was independently associated with the increased risk of CVD in T2DM. For non-diabetics, decreased slope of 24 h SBP-HR, and decreased correlation of 24 h SBP-HR were associated with increased risk of CVD. In conclusion, increased HR variability during sleep was a predictor for incident CVD in T2DM, but not in non-diabetics. Increased HR variability at night would reflect pathophysiological mechanism of T2DM.