Aims Anterior T-wave inversion (TWI) is a recognized variant in athletes of African/Afro Caribbean origin and some endurance athletes; however, the presence of this specific repolarization anomaly also raises the possibility of cardiomyopathy. The differentiation between physiological adaptation and cardiomyopathy may be facilitated by examining other repolarization parameters, notably the J-point and the ST-segment. Methods and results We compared the electrocardiogram pattern of anterior TWI in a series of 80 healthy athletes (median age 21 years, 75% males); 95 patients with hypertrophic cardiomyopathy (HCM) (median age 46 years, 75% males), including 26 affected athletes; and 58 patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) (median age 32 years, 71% males), including 9 affected athletes. Athletes and patients were of either white/Caucasian or black/Afro Caribbean descent and showed TWI >= 1 mmin >= 2 contiguous anterior leads (V1-V4). We aimed to identify repolarization patterns for differentiating physiologic from pathologic TWI. After adjustment for age, gender, and ethnicity, J-point elevation,1 mm (but no ST-segment elevation without J-point elevation) in the anterior leads showing TWI and TWI extending beyond V4 remained independent predictors for both ARVC, with OR = 569 (95% CI = 38-8545; P < 0.001) and OR = 6.0 (95% CI = 1.2-37.8; P = 0.03), respectively, and HCM with OR = 227 (95% CI = 12-1620; P < 0.001) and OR = 331 (95% CI = 20-2752; P = 0.001), respectively. In athletes with anterior TWI, the combination of J-point elevation = 1 mm and TWI not extending beyond V4 excluded a cardiomyopathy, either ARVC or HCM, with 100% sensitivity and 55% specificity. Conclusion The combination of J-point elevation and TWI confined to lead V1-V4 offers the potential for an accurate differentiation between 'physiologic' and 'cardiomyopathic' anterior TWI, among athletes of both white/Caucasian or black/Afro Caribbean descent. Conversely, ST-segment elevation without J-point elevation preceding anterior TWI may reflect cardiomyopathy.