Peripheral chemoreflex mediated increases in both parasympathetic and sympathetic drive under chronic hypoxia may evoke brady-arrhythmias during apneic periods. We determined if: a) voluntary apnea unmasks arrhythmia at low (344m) and high (5050m) altitude, b) if high altitude natives (Nepalese Sherpa) exhibit similar cardiovagal responses at altitude; and c) if brady-arrhythmias at altitude are partially chemoreflex mediated. Participants were grouped as Lowlanders (n=14; age=27±6yrs) and Nepalese Sherpa (n=8; age=32±11yrs). Lowlanders were assessed at 344m and 5050m while Sherpas were assessed at 5050m. Heart rate (HR) and rhythm (Lead-II ECG) were recorded during rest and voluntary end-expiratory apnea. Peripheral chemoreflex contributions were assessed in Lowlanders (n=7) at altitude after 100% oxygen. Lowlanders had higher resting HR at altitude (70±15 vs. 61±15 bpm;P<0.01) that was similar to Sherpas (71±5 bpm;P=0.94). High-altitude apnea caused arrhythmias in 11 of 14 Lowlanders (junctional rhythm (n=4), 3° atrio-venticular block (n=3), sinus pause (n=4)) not present at low altitude and larger marked bradycardia (nadir -39±18 bpm; P<0.001). Sherpas exhibited a reduced bradycardia response during apnea compared to Lowlanders (P<0.001) and did not develop arrhythmias. Hyperoxia blunted bradycardia (nadir -10 ±14bpm; P<0.001 compared to hypoxic state) and reduced arrhythmia incidence (3 of 7 Lowlanders). Degree of bradycardia was significantly related to hypoxic ventilatory response (HVR) at altitude and predictive of arrhythmias (P<0.05). Our data demonstrates apnea-induced brady-arrhythmias in Lowlanders at altitude but not in Sherpa (potentially through cardio-protective phenotypes). The chemoreflex is an important mechanism in genesis of brady- arrhythmias and the HVR may be predictive for identifying individual susceptibility to events at altitude.