Introduction: In order to enhance e-learning, the first online educational course for teaching Medline, was established in Isfahan University of Medical Sciences. This study was designed to compare the effectiveness of online, face to face and combined educational methods presented for medical students. Methods: In an experimental study, Medline was taught to 40 medical students by three methods of online, face to face and combined educational methods and then, their knowledge, skills and satisfaction rate were measured and compared. The data collection tools included a questionnaire consisted of 10 multiple choice questions for measuring knowledge, a checklist for assessing participants’ skills in searching strategies, the appropriateness of the found articles for the subject and the time length for searching, and a ten item questionnaire with five point Likert scale for measuring their satisfaction. The data was analyzed by chi2, t-test, ANOVA and Kruskal–Wallis through SPSS software. Results: The mean and standard deviation of students’ knowledge in face to face, online and combined educational methods were 75 ±16, 70 ± 21 and 82.2±13 out of 100, respectively. The mean and standard deviation of their skills in face to face, online and combined educational methods were 76.9±25, 70±24 and 90.7±11 out of 100, respectively. There was no significant difference between the scores of knowledge and skills of the three groups. Also, students' satisfaction showed no significant difference in the three groups. Conclusion: It seems that, for expanding E-learning, a combination of online and face to face guidance can possibly have an acceptable effectiveness. Meanwhile, for achieving such combined method, the appropriate ground, containing related hardware and software must be provided in universities.