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Introduction The electrocardiogram (ECG) is one of the most important tools in diagnosing cardiac abnormalities, particularly arrhythmias and myocardial infarction. It is one of the certifiable competencies for final-year medical undergraduate students. We determined virtual reality's effectiveness in acquiring and retaining ECG interpretation skills among medical students compared to traditional teaching. Methods One hundred and forty students were randomized into two groups. Seventy-one students (immersion group) were trained using virtual reality simulation to acquire and retain interpretation skills of normal and abnormal ECG. Sixty-nine students (traditional group) were trained in the classroom using chalk and board. The primary outcome of change in acquiring knowledge of the interpretation of ECG was determined by comparing pre and post-test scores. The secondary outcome of retention of knowledge was determined by comparing pre-test and second post-test scores conducted after eight weeks of intervention. The p-value of <0.05 was considered significant. Results Out of 140 students, 50 (35.7%) were males and 90 (64.3%) were female. The mean age of the students was 22.1 (SD 1.1), with 69.3% of them between the ages of 21 and 22 years. Mean pre-test scores for the interpretation of normal ECG among immersion and traditional groups were 9.8 (SD 8.4) and 8.3 (SD 7.5), respectively, and post-test scores for the acquisition of knowledge were 24.3 (SD 5.5) and 24.8 (SD 6.3), respectively. The post-test scores for retention skills were 25.3 (SD 5.6) and 20.7 (SD 6.9) respectively (p<0.001). The mean pre-test scores for the interpretation of abnormal ECG of both groups were 7.0 (SD 6) and 8.3 (SD 6.6), respectively. Mean post-test scores for acquiring knowledge to interpret abnormal ECG were 23.5 (SD 6.2) and 17.7 (SD 9), respectively (p<0.001), and mean post-test scores for retention of interpretation skills of abnormal ECG were 19.2 (SD - 6.9) and 13.3 (SD 10.2) respectively (p=0.001). The pairwise comparison of the immersion group indicates that all the combinations that changed in score from the pre to post-intervention time points, from pre-to-retention time, and from the post-to-retention time were significant (p<0.001). Conclusion Virtual reality teaching had a better impact on acquiring and retaining the skill for interpreting normal and abnormal electrocardiograms., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institute Ethics Committee of Pondicherry Institute of Medical Sciences issued approval sd. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iqbal et al.)