BACKGROUND Major adverse cardiac and cerebrovascular event (MACCE) is one of most common complications of hemodialysis patients. Heart rate variability (HRV) is the predictor of death in heart disease patients. However, there are no studies on the role of HRV in hemodialysis patients. METHODS From September 2009 to March 2011, 24-h electrocardiography was performed in 101 hemodialysis patients. Standard deviation of sequential 5-minute N-N interval means (SDANN) and standard deviation of the N-N interval (SDNN) was examined by a 24-h ECG analysis. Patients were observed prospectively. The primary endpoints were incidence of MACCE and MACCE-free survival. RESULTS We studied 90 hemodialysis patients (64 males, 63.4 ± 11.8 years old). During a follow-up period of 32.0 ± 11.7 months, 33 patients developed MACCE. 24-h ECG showed mean SDNN 93.4 ± 33.4 ms and mean SDANN 83.2 ± 31.3 ms. MACCE group showed significantly lower SDNN and SDANN than event-free group. In Kaplan-Meier analysis higher SDNN and SDANN group showed significantly higher event-free survival rate than lower group. Using a Cox proportional hazards model, SDNN was independent prognostic factor while SDANN or diabetic status was not significant. In diabetic cases, there were no differences in any factors for the incidence of MACCE between higher SDNN, SDANN groups and lower groups. On the other hand in non-diabetic cases, lower SDNN or SDANN group developed significantly higher MACCE than higher groups. CONCLUSIONS Measurement of HRV by Holter ECG is useful to predict MACCE in hemodialysis patients, especially non-diabetic group.