Background: High sympathetic tone creates a significant risk for ventricular arrhythmias and sudden death, which can especially affect patients after a myocardial infarction (MI) when exercising in a hypoxic environment. Methods and Results: The 16 patients after MI and 10 normal volunteers (NV) underwent a 1-day trip from low altitude (540 m, Bern) to high altitude (3,564 m Jungfraujoch, Swiss Alps). Autonomic function under resting and mental stress conditions at low and high altitude was assessed. MI patients demonstrated a significantly lower stroke volume (P<0.05) at rest compared with the NV at low as well as high altitude. High altitude exposure was accompanied by higher low-frequency/high-frequency values in the MI patients compared with NV (P<0.01). Following mental stress, MI patients failed to show the normal return to resting values at high altitude, suggesting sustained sympathetic and diminished parasympathetic activation during post-stress recovery. Conclusions: Although all MI patients were either on β-blockers or AII inhibitors, they showed higher sympathetic activity during exposure to high altitude compared with NV. In addition, the respective parasympathetic tone was reduced, especially during recovery. This puts patients after MI at an increased risk for cardiac arrhythmias and they should be advised of this if going to high altitudes. (Circ J 2009; 73: 1485 - 1491)