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Although cardiovascular screening is recommended for athletes before participating in sports, the role of 12-lead electrocardiography (ECG) remains uncertain. To date, no prospective data that compare screening with and without ECG have been available.To compare the performance of preparticipation screening limited to medical history and physical examination with a strategy that integrates these with ECG.Cross-sectional comparison of screening strategies.University Health Services, Harvard University, Cambridge, Massachusetts.510 collegiate athletes who received cardiovascular screening before athletic participation.Each participant had routine history and examination–limited screening and ECG. They received transthoracic echocardiography (TTE) to detect or exclude cardiac findings with relevance to sports participation. The performance of screening with history and examination only was compared with that of screening that integrated history, examination, and ECG.Cardiac abnormalities with relevance to sports participation risk were observed on TTE in 11 of 510 participants (prevalence, 2.2%). Screening with history and examination alone detected abnormalities in 5 of these 11 athletes (sensitivity, 45.5% [95% CI, 16.8% to 76.2%]; specificity, 94.4% [CI, 92.0% to 96.2%]). Electrocardiography detected 5 additional participants with cardiac abnormalities (for a total of 10 of 11 participants), thereby improving the overall sensitivity of screening to 90.9% (CI, 58.7% to 99.8%). However, including ECG reduced the specificity of screening to 82.7% (CI, 79.1% to 86.0%) and was associated with a false-positive rate of 16.9% (vs. 5.5% for screening with history and examination only).Definitive conclusions regarding the effect of ECG inclusion on sudden death rates cannot be made.Adding ECG to medical history and physical examination improves the overall sensitivity of preparticipation cardiovascular screening in athletes. However, this strategy is associated with an increased rate of false-positive results when current ECG interpretation criteria are used.None.