PURPOSE: Evidence suggests acute mountain sickness (AMS) aligns to heart rate variability (HRV) suppression at high altitude. This study explored associations between measures of autonomic cardiac function and AMS scores in normobaric hypoxia (NH) and during ascent to very high altitude in the natural environment. METHODS: Thirty participants (17 male and 13 female, aged 20-62 years) trekked from 2800m to 5350m (Himalaya, Nepal) over 14 days. Short term temporal and spectral measures of HRV were recorded at rest (paced breathing, 12 breaths per minute), in NH (FIO2=0.124, ~4100m) and in hypobaric hypoxia (HH) at 4356m and 5350m, during ascent. RMSSD and 60 second heart rate recovery (HRR60) following stepping exercise (3 min at 50-60% maximal aerobic capacity) were accepted measures of parasympathetic neural activity. The heart rate response (∆HR) to an orthostatic postural challenge (two minutes supine followed by two minutes standing), reflective of sympathetic neural activity, was measured at the same time points (∆HR = HR [peak stand] - HR [mean supine]). AMS diagnosis was confirmed for scores ≥ 5.0 (Lake Louise Survey, LLS) or ≥ 0.70 (Environmental Symptoms Questionnaire, ESQ-c) at least once during the ascent. Institutional ethical approval was gained. RESULTS: Data analysis reflects 24 participants. Eleven (46%) developed AMS. Peak LLS AMS scores ranged between 1-5, 0-10 and 2-11 units in the AMS group at 2800m, 4356m and 5350m respectively, and 0-4 for the non-AMS group. No significant interaction (P=0.161) nor a main effect for altitude (P=0.093) was observed, however a significantly greater LLS score was observed in the AMS group at 5300m (P<0.001). Peak LLS scores at 2800m correlated with RMSSD (NH) (r=.483, P=.020) and at 4300m correlated with RMSSD at 4300m (-.487, P=.025). Postural ∆HR at 2800m correlated significantly with the ESQ-c and peak LLS scores at 4300m (r=-.601, P=.002 and r=-.579, P=.004), and the ∆HR at 4300m correlated with ESQ-c and LLS scores at 4300m (r=.-570, P=.005 and r=-.471, P=.023). HRR60 (NH) correlated with LLS score at 4300 m and peak LLS score at this altitude (r=-.495, P=.026 and r=-.450, P=.047 respectively). CONCLUSION: AMS-susceptible individuals show vagal suppression at high altitude. Vagal measures may be useful indicators for AMS susceptibility at very high altitude.