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Objective To evaluate the outcomes of pre-participation cardiovascular screening among National Collegiate Athletic Association (NCAA) athletes and quantify the added value of history and physical exam (H&P) when combined with a screening ECG.Design Systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sources MEDLINE (1946–present), EMBASE (1947–present), PubMed (1966–present) and Cochrane Library (1991–present).Eligibility criteria for selecting studies Peer-reviewed research articles published in English reporting original findings on pre-participation cardiovascular screening outcomes in NCAA athletes.Results 18 studies, representing 27 891 NCAA athletes (44.2% female), were included. A total of 66 (0.24%) athletes were diagnosed with a cardiovascular condition associated with serious morbidity or sudden cardiac arrest/death (SCA/D). Wolff-Parkinson-White was the most common diagnosis (n=39, 59.1%), followed by hypertrophic cardiomyopathy (n=11, 16.7%). Among the eight studies (16 609 athletes) for which the screening performance of ECG and H&P could be extracted separately, ECG screening resulted in a 3.5-fold higher detection rate of true positive cases (number needed to screen (NNS) =475) compared with H&P alone (NNS=1661). The false positive rate for H&P was 17% versus 5% for ECG (p<0.001). The added value of H&P in athletes with a negative ECG was low (NNS=3003).Conclusion ECG screening significantly increases the detection of conditions associated with serious morbidity or SCA/D compared with H&P alone, with H&P providing minimal added value in athletes with a normal ECG. Our findings support the utility of ECG in preparticipation screening for NCAA athletes.PROSPERO registration number CRD42020188308.