Synchronous distance education (SDE) has recently been widely used for medical students. The purpose of this study was to compare the effects of SDE with traditional face-to-face education (TE) on the learning outcomes of undergraduate medical students. Participants were class enrolled in 2015 and class enrolled in 2016. The entire 2 classes (n = 148), when they were a 6th-year grade at a medical college, were invited to participate in the case-controlled study. The 6th-grade curriculum includes 5 courses in ophthalmology, otorhinolaryngology, dentistry, traditional Chinese medicine, and dermatology. Outcomes included postintervention exams evaluating the knowledge gained from the 5 courses, a self-assessment of learning based on examinable learning objectives, student satisfaction, learning behavior, and teacher-student communication. Sixty-nine students (SDE n = 39, TE n = 30) participated in the outcome assessments. The mean score of the otolaryngology course and the dermatology course in the SDE group was higher than the TE group (P < .05). Other courses and combined grades for the 5 courses were without statistical differences between the 2 groups. Of the 12 self-assessment learning objectives, 10 were significantly more positive in the SDE group than in the TE group. There was no statistical difference between the 2 groups regarding student satisfaction. The SDE group was more engaged than the TE group in the corresponding department apprenticeship after the theory class. The attendance rate and concentration in the class of the SDE group were comparable to the TE group. Students in the SDE group spoke more often in class and had a higher level of student-teacher communication than the TE group. The SDE is a teaching tool that can replace TE in the theoretical teaching of medical courses.