Peripheral blood stem cell harvest (PBSCH) has been widely performed for rescue following high-dose chemotherapy or as an alternative to BMT for allogeneic stem cell transplantation. However, severe complications, which caused sudden death, were reported in PBSCH from healthy donors. Recent cumulative evidence shows that decrease in cardiovascular signal variability of the R-R period (heart rate variability, HRV) is strongly associated with sudden death and/or cardiac event after a myocardial infarction. Furthermore, usefulness of HRV as a clinical tool has been explored in numerous conditions such as hypertrophic cardiomyopathy, obstructive sleep apnea, diabetic neuropathy, and various neurological alterations. Two types, time domain and frequency domain, are included in HRV analysis. In this study, we investigated HRV during and after apheresis for PBSCH in 23 cases [8 autologous transplant patients, 15 allogeneic transplant donors; 8 men, 15 women; median age 47 years (27–55)]. Date from 24-hour ambulatory ECG recordings were analyzed with R-R data analysis software (MemCalc/CHIRAM version 1, Suwatrust, Tokyo, Japan). Acknowledged simple markers in time domain analysis are the standard deviation of all normal beats (SDNN) and the square root of the mean of the sum of squared differences between adjacent normal-to-normal intervals (r-MSSD). On the other hand, markers in frequency domain analysis include LH, low frequency power (0.04–0.15Hz); HF, high frequency power (0.15–0.4 Hz); LH/HF ratio; VLF, very low frequency power (0.003–0.04 Hz); and ULF, ultra low frequency power (<0.0033 Hz). These power spectrum analyses of HRV are used to investigate sympathovagal balance, autonomic cardiovascular control and/or target function impairment. Among frequency domain analysis markers, VLF or ULF reportedly have particular prognostic value in all causes of mortality after myocardial infarction. In our study, SDNN, r-MSSD, HF, VLF, and ULF significantly and markedly decreased to morbid levels during apheresis (all P<0.001). Of 23 harvest cases, symptomatic hypotension occurred during apheresis in 2 cases and after apheresis in one case. Notably, in these 3 cases, SDNN and VLF had already begun to decrease about 5–10 minutes before significant symptomatic hypotension occurred (P=0.03, P=0.04, respectively). Our results suggested that morbidly decreased HRV indicates serious cardiovascular load and suppression of the parasympathetic nervous system in apheresis for PBCSH. HRV analysis might be a useful tool to prevent donors from severe autonomic cardiovascular complications in PBCSH.