Purpose: The purpose of this study is to develop a course to teach through problem-based learning the use of antibiotics during an internal medicine clerkship, and to evaluate the responses of students to it. Methods: The course was designed to teach third-year medical students how to prescribe antibiotics to be given to real patients. A qualitative evaluation for the modified problem-based learning was performed by tutor’s observation and focus group interview, and a quantitative evaluation by questionnaires before and after the course. Results: Seventy-nine students experienced the modified problem-based learning during the infectious disease section of an internal medicine clerkship. Most students participated actively and gave a positive evaluation expressing a need for problem-based learning on prescribing antibiotics. The course significantly increased the students’ self-confidence in both approaching patients and prescribing antibiotics. Conclusion: Modified problem-based learning is a useful educational tool in clinical clerkship.