Objectives It remains unclear whether computer-assisted instruction (CAI) is more effective than other teaching methods in acquiring and retaining ECG competence amongst medical students and residents. Design This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data sources Electronic literature searches of PubMed, databases via EBSCOhost, Scopus, Web of Science, Google Scholar and grey literature were conducted on 28 November 2017. We subsequently reviewed the citation indexes of articles identified by the search. Eligibility criteria Studies were included if a comparative research design was used to evaluate the efficacy of CAI versus other methods of ECG instruction, as determined by the acquisition and/or retention of ECG competence of medical students and/or residents. Data extraction and synthesis Two reviewers independently extracted data from all eligible studies and assessed the risk of bias. After duplicates were removed, 559 papers were screened. Thirteen studies met the eligibility criteria. Eight studies reported sufficient data to be included in the meta-analysis. Results In all studies, CAI was compared to face-to-face ECG instruction. There was a wide range of computer-assisted and face-to-face teaching methods. Overall, the meta-analysis found no significant difference in acquired ECG competence between those who received computer-assisted or face-to-face instruction. However, sub-analyses showed that CAI in a blended learning context was better than face-to-face teaching alone, especially if trainees had unlimited access to teaching materials and/or deliberate practice with feedback. There was no conclusive evidence that CAI was better than face-to-face teaching for longer-term retention of ECG competence. Conclusion CAI was not better than face-to-face ECG teaching. However, this meta-analysis was constrained by significant heterogeneity amongst studies. Nevertheless, the finding that blended learning is more effective than face-to-face ECG teaching is important in the era of increased implementation of e-learning. PROSPERO registration number CRD42017067054