Background This study compares the accuracy of cardiovascular screening in active adolescents and young adults using a standardised history, physical examination and resting 12-lead ECG. Methods Participants were prospectively screened using a standardised questionnaire based on the Preparticipation Physical Evaluation Monograph 4th Edition (PPE-4), physical examination and ECG interpreted using modern standards. Participants with abnormal findings had focused echocardiography and further evaluation. Primary outcomes included disorders associated with sudden cardiac arrest (SCA). Results From September 2010 to July 2011, 1339 participants underwent screening: age 13-24 (mean 16) years, 49% male, 68% Caucasian, 17% African- American and 1071 (80%) participating in organised sports. Abnormal history responses were reported on 916 (68%) questionnaires. After physician review, 495/ 916 (54%) participants with positive questionnaires were thought to have non-cardiac symptoms and/or a benign family history and did not warrant additional evaluation. Physical examination was abnormal in 124 (9.3%) participants, and 72 (5.4%) had ECG abnormalities. Echocardiograms were performed in 586 (44%) participants for abnormal history (31%), physical examination (8%) or ECG (5%). Five participants (0.4%) were identified with a disorder associated with SCA, all with ECG-detected Wolff-Parkinson-White. The falsepositive rates for history, physical examination and ECG were 31.3%, 9.3% and 5%, respectively. Conclusions A standardised history and physical examination using the PPE-4 yields a high false-positive rate in a young active population with limited sensitivity to identify those at risk for SCA. ECG screening has a low false-positive rate using modern interpretation standards and improves detection of primary electrical disease at risk of SCA.