Side effects of varying severity are frequent in peripheral blood stem cell harvest (PBSCH). Life-threatening complications associated with PBSCH have also been reported. Heart rate variability (HRV), which reflects sympathovagal balance and autonomic cardiovascular control, has been a subject of intense interest in various diseases precipitating sudden death. Here, we prospectively assessed the impact of leukapheresis on HRV among autologous hematopoietic cell transplant patients and healthy donors. We found that HRV indicators, the standard deviation of normal-to-normal intervals (SDNN) value, the square root of the mean of the sum of squared differences between the adjacent normal-to-normal interval (r-MSSD) value, total frequency (TF), high frequency (HF) and low frequency (LF) powers decreased significantly to morbid levels during leukapheresis (all P < 0.01). Morbid changes in SDNN value, TF and LF powers were significantly sustained for 6-9 h after leukapheresis (all P < 0.05). Furthermore, TF and LF powers prior to leukapheresis were significantly lower in subjects with symptomatic hypotension than in the other subjects [3282 (3121-4427) vs. 6018 (4983-9816) ms(2), P = 0.03; 93 (42-144) vs. 237 (142-360) ms(2), P = 0.03, respectively]. Our results suggest that HRV analysis might be of use in evaluating and predicting the adverse effects of cardiovascular complications in PBSCH.