BACKGROUND: Hypertrophic cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death in athletes. However, preparticipation ECG screening has often been criticized for failing to meet cost-effectiveness thresholds, in part because of high false-positive rates and the cost of ECG screening itself. OBJECTIVE: The purpose of this study was to assess the testing characteristics of an automated ECG algorithm designed to screen for HCM in a multi-institutional pediatric cohort. METHODS: ECGs from patients with HCM aged 12 to 20 years from 3 pediatric institutions were screened for ECG criteria for HCM using a previously described automated computer algorithm developed specifically for HCM ECG screening. The results were compared to a known healthy pediatric cohort. The studies then were read by trained electrophysiologists using standard ECG criteria and compared to the results of automated screening. RESULTS: One hundred twenty-eight ECGs from unique patients with phenotypic HCM were obtained and compared with 256 studies from healthy control patients matched in 2:1 fashion. When presented with the ECGs, the non-voltage-based algorithm resulted in 81.2% sensitivity and 90.7% specificity. A trained electrophysiologist read the same data according to the Seattle Criteria, with 71% sensitivity with 95.7% specificity. The sensitivity of screening as well as the components of the ECG screening itself varied by institution. CONCLUSION: This pilot study demonstrates a potential for automated ECG screening algorithms to detect HCM with testing characteristics similar to that of a trained electrophysiologist. In addition, there appear to be differences in ECG characteristics between patient populations, which may account for the difficulties in universal screening.