Abstract Introduction Negative T waves at ECG represent a common diagnostic dilemma in athletes. These subjects, often asymptomatic, undergo ECG screening every year before practicing competitive sports. The clinical meaning of these ECG abnormalities is often unclear and a comprehensive diagnostic evaluation is needed. Echocardiography is the first step test in all these cases, but the advent of cardiac MRI in the clinical field empowers the diagnostic capability for the identification of cardiovascular disease at a very early stage, even when transthoracic echocardiography is normal. The aim of the present study is to define the prevalence of positive cardiac MRI among athletes with negative T waves at ECG and normal echocardiography and to define the clinical predictors of pathological cardiac MRI or cardiac CT Material and Methods A consecutive cohort of athletes with negative T waves at ECG and normal findings at transthoracic echocardiography were enrolled. All athletes underwent 24h ECG monitoring, ECG exercise test and cardiac MRI; cardiac CT was performed only if clinically indicated and in all subjects with >35 years old of age. The type of sport practiced was recorded and stratified according to intensity into low- mid- and high-intensity. The site of negative T waves was recorded and T waves were defined as “deep” if wider than 2 mm. The presence of any arrhythmias during the 24-ECG monitor or exercise ECG test was recorded as well. The primary end-point of the study was the identification of diagnostic criteria for any structural heart disease at cardiac MRI or cardiac CT Results A total of 55 athletes (50 male, 90%) were enrolled with a mean age of 27 ± 14 years-old. Most of them practiced high-intensity sports activity (47 athletes, 85.4%). Anterior T waves were the most common type (29 athletes, 52.7%) and 8 athletes (14.5%) had more than isolated ventricular ectopic beats at 24-hours ECG monitoring. Among the entire cohort, 16 athletes (29.1%) had cardiac MRI or cardiac CT diagnostic for specific structural heart disease. Of interest, the presence of deep negative t waves (OR 8.1 95%CI 1.4–49.5, p<0.001) and arrhythmias more complex than isolated ventricular ectopic beats (OR 5.5 95%CI 1.1–26.6, p<0.001) were significative associated with structural heart disease even in the presence of normal transthoracic echocardiography. Conclusions Our results identified a prevalence of 29% of structural heart disease among athletes with negative T waves at ECG even when transthoracic echocardiography was normal. Of interest deep negative T waves and arrhythmias more complex than isolated ventricular ectopic beats were significative associated with structural heart disease. Thus, according to our results, advanced cardiovascular imaging techniques (cardiac MRI or cardiac CT) should be considered in athletes with negative T waves at ECG even in the presence of normal transthoracic echocardiography especially if complex ventricular arrhythmias of deep negative T waves are present.