There is evidence suggesting that high altitude (HA) exposure leads to a fall in heart rate variability (HRV) that is linked to the development of acute mountain sickness (AMS). The effects of sex on changes in HRV at HA and its relationship to AMS are unknown. METHODS: HRV (5-min single-lead ECG) was measured in 63 healthy adults (41 men and 22 women) 18-56 yr of age at sea level (SL) and during a HA trek at 3619, 4600, and 5140 m, respectively. The main effects of altitude (SL, 3619 m, 4600 m, and 5140 m) and sex (men vs women) and their potential interaction were assessed using a factorial repeated-measures ANOVA. Logistic regression analyses were performed to assess the ability of HRV to predict AMS. RESULTS: Men and women were of similar age (31.2 +/- 9.3 vs 31.7 +/- 7.5 yr), ethnicity, and body and mass index. There was main effect for altitude on heart rate, SD of normal-to-normal (NN) intervals (SDNN), root mean square of successive differences (RMSSD), number of pairs of successive NN differing by >50 ms (NN50), NN50/total number of NN, very low-frequency power, low-frequency (LF) power, high-frequency (HF) power, and total power (TP). The most consistent effect on post hoc analysis was reduction in these HRV measures between 3619 and 5140 m at HA. Heart rate was significantly lower and SDNN, RMSSD, LF power, HF power, and TP were higher in men compared with women at HA. There was no interaction between sex and altitude for any of the HRV indices measured. HRV was not predictive of AMS development. CONCLUSIONS: Increasing HA leads to a reduction in HRV. Significant differences between men and women emerge at HA. HRV was not predictive of AMS.