Several methods of heart rate-adjusted ST segment (ST/HR) analysis have been suggested to improve the diagnostic accuracy of exercise electrocardiography in the identification of coronary artery disease compared with traditional ST segment analysis. However, no comprehensive comparison of these methods on a lead-by-lead basis in all 12 electrocardiographic leads has been reported. This article compares the diagnostic performances of ST/HR hysteresis, ST/HR index, ST segment depression 3 minutes after recovery from exercise, and ST segment depression at peak exercise in a study population of 128 patients with angiographically proved coronary artery disease and 189 patients with a low likelihood of the disease. The methods were determined in each lead of the Mason-Likar modification of the standard 12-lead exercise electrocardiogram for each patient. The ST/HR hysteresis, ST/HR index, ST segment depression 3 minutes after recovery from exercise, and ST segment depression at peak exercise achieved more than 85% area under the receiver-operating characteristic curve in nine, none, three, and one of the 12 standard leads, respectively. The diagnostic performance of ST/HR hysteresis was significantly superior in each lead, with the exception of leads a VL and V1. Examination of individual leads in each study method revealed the high diagnostic performance of leads I and -aVR, indicating that the importance of these leads has been undervalued. In conclusion, the results indicate that when traditional ST segment analysis is used for the detection of coronary artery disease, more attention should be paid to the leads chosen for analysis, and lead-specific cut points should be applied. On the other hand, ST/HR hysteresis, which integrates the ST/HR depression of the exercise and recovery phases, seems to be relatively insensitive to the lead selection and significantly increases the diagnostic performance of exercise electrocardiography in the detection of coronary artery disease.