Early repolarization (ER) is typically observed in highly trained athletes as a physiologic consequence of increased vagal tone. The variant of anterior (V1 to V3) ER characterized by “domed” ST-segment elevation and negative T wave raises problems of differential diagnosis with the “coved-type” electrocardiographic pattern seen in Brugada syndrome (BS). This study was designed to identify electrocardiographic criteria for distinguishing athlete's ER from BS. The study compared the electrocardiographic tracings of 61 healthy athletes (80% men, median age 23 ± 8 years), showing “domed” ST-segment elevation and negative T wave in leads V1 to V3, with those of 92 consecutive age- and sex-matched BS patients with a “coved-type” electrocardiographic pattern. The electrocardiographic analysis focused on the ST-segment elevation at J point (ST_J) and at 80 milliseconds after J point (ST₈₀). Athletes had a lower maximum amplitude of ST_J (1.46 ± 0.7 vs 3.25 ± 0.6 mm, p <0.001) and lower ST_J/ST₈₀ (0.8 ± 0.3 vs 1.6 ± 0.3, p <0.001). All patients (100%) with BS showed a downsloping ST-segment configuration (ST_J/ST₈₀ >1) versus only 2 (3%) athletes (p <0.001). An upsloping ST-segment configuration (ST_J/ST₈₀ <1) showed a sensitivity of 97%, a specificity of 100%, and a diagnostic accuracy of 98.7% for the diagnosis of ER. At multivariate analysis, ST_J/ST₈₀ ratio remained the only independent predictor for ER (odds ratio 87, 95% confidence interval 19 to 357, p <0.001). In conclusion, the ST_J/ST₈₀ ratio is a highly accurate electrocardiographic parameter for differential diagnosis between anterior ER of the athlete and BS. Our results may help in reducing the number of athletes who undergo expensive diagnostic workup or are unnecessarily disqualified from competition for changes that fall within the normal range of athlete's heart.