Introduction This study investigated medical students’ intended learning outcomes based on e-learning and in-person education. Methods In this cross-sectional comparative analytical study, a group of 126 undergraduate medical students’ intended learning outcomes under two different teaching methods, including e-learning and in-person, were repeatedly measured based on the census sampling method. Participants were in the preclinical curriculum phase (physiopathology) at Mashhad University of Medical Sciences (MUMS), Iran. Due to expert panel opinion, the same medical teachers and similar difficulty of lessons were considered in two investigated academic semesters. In addition, difficulty and discrimination indexes of formative and summative assessments were controlled for two study groups. The students’ learning outcome index was the knowledge test scores participants received in the relevant lessons of the General Medicine (GM) curriculum preclinical courses. Results The findings indicated that students learning outcomes were significantly higher during e-learning than in in-person education for all examined variables (P < 0.05). Moreover, the difference between students’ Grade Point Average (GPA) categories among the two groups was significant (P = 0.022). Students with a GPA of less than 14 experienced higher increments in their average scores after the e-learning compared to in-person education. Compared to face-to-face courses, improvements in pharmacology, theoretical semiology, and pathology scores after e-learning courses were statistically significant (P < 0.001). The differences in mean scores related to practical pathology and semiology in the two approaches were not statistically significant, P = 0.624 and P = 0.149, respectively. Furthermore, the overall students’ average scores increased significantly during e-learning versus in-person education (P < 0.001). Conclusion We concluded that e-learning could be appreciated as a successful method of medical education and can be used as an alternative educational method. However, considering the importance of practical or clinical courses in medical education, further research about the efficacy of the e-learning approach is highly recommended.
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