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Background: Since the emergence of coronavirus diseases 2019 (COVID-19) not only have social and the economical dimension of life been disturbed but it has also shattered educational activities as well. Due to fear of disease spread educational institutes are forced to implement online educational systems to teach their pupils. This study aims to explore the student's perceptions related to E-learning and their positive and negative outcome among medical students in Pakistan and Iran., Method: ology : This cross-sectional questionnaire-based study was conducted at Rawalpindi Medical University, Rawalpindi, Pakistan, and Islamic Azad University of Medical Sciences Tehran, Iran. This study involved 402 medical students of Rawalpindi Medical University, Rawalpindi, Pakistan (n = 202), and Islamic Azad University of Medical Sciences Tehran, Iran (n = 200) who were actively involved in the online mode of education. A self-administered validated questionnaire was used for data collection. Descriptive statistics and chi-square analysis was used and analysis was done through SPSS V.23. A P-value of 0.05 was taken as significant., Results: A total of 402 students were enrolled, 202 from Pakistan and 200 from Iran. About 68.2% of the students were acquainted with moderate levels of IT skills. About 75.8% of the students were not showing any previous experience with E-learning. The most common advantage of E-learning was the ability to stay at home. The technical problem was the most common disadvantage in our study. Finally, face-to-face learning in terms of increasing knowledge, skill, and social competence was considered the best mode of learning both by Pakistani and Irani students. Country-wise effectiveness of face-to-face learning in terms of increasing knowledge is statistically significant (p-value = 0.019). Acceptance of E-learning is statistically associated with the country of learning (p-value = 0.020). E-learning was rated as enjoyable by 51.5% of the students., Conclusion: E-learning has its associated advantages and disadvantages as perceived by medical students but still face-to-face learning is considered the most effective form of learning as responded by medical students., Competing Interests: All authors declared no conflict of interest., (© 2022 The Authors.)