Objective To assess the effect of altitude hypoxia on the elderly patients with coronary artery disease (CAD). Methods Three subject groups were surveyed during their train trip on the highest railroad——the Qinghai-Tibet Railway: 22 elderly individuals with documented CAD, 20 healthy elderly controls, and 20 healthy young controls, all of whom from Beijing near the sea level (76 m). Survey questions addressed clinical features of their healthy conditions and aspects of their coronary disease. The baseline study was performed at Xining at an altitude of 2261m, and then during acute exposure to altitudes of 2808 m, 4768m, 5072 m and 4257 m by train for 24 hours. Resting pulse rate, blood pressure, oxygen saturation, electrocardiograph (ECG), and cardiac work estimated by the heart rate-blood pressure double product were obtained five times in each subject at different altitudes. Results On arrival to altitudes between 4768 m and 5072 m, the older passengers, especially those with preexisting coronary disease, had higher HR, higher BP, and lower SaO2, as well as more frequent abnormalities on ECG, as compared to the younger healthy subjects. As compared with the healthy elderly controls, incomplete right bundle branch block, left ventricular hypertrophy, and ST segment depression were more frequently seen in the elderly coronary patients (P<0.01). Cardiac work in group 1 was increased by 13% 12 hours after arrival to altitudes between 2808 m and 5072 m. Oxygen saturation decreased significantly with the altitude increasing by train ascent but improved after inhalation of oxygen. Most of the older subjects tolerated their sojourn at high altitude well except one who developed angina repeatedly with a significant ST segment depression. Conclusions Coronary events and ECG signs of myocardial ischemia are rare in elderly individuals with CAD who travel from sea level to moderate altitudes of 1500m to 2800 m. Patients with CAD who are well compensated at sea level generally tolerate this moderate altitude well. However, it would be prudent for patients with CAD going to altitude above 3000 m. The patients should consult their physician before undertaking a trip to such altitude.