Background and purpose: Studies have shown the advantages of e-CME programs. Developing case-based e-CME activities, which is a popular format of e-CME programs, is difficult and time-consuming. In this article, we have discussed our experience in designing instructional system for creating case-based e-CME contents.Methods: We designed the instructional system in five steps (i.e., system analysis, design, development, delivery, and evaluation) to create e-contents. We held several sessions with subject experts to analyze the system. Then, we determined the contents’ framework and created a plan for faculty members’ development and incentives. In the development phase, we held workshops for faculty members and trained e-learning advisors who were to help faculties create contents. Incentives were legitimized. Then, we delivered programs to the learners who would fill a program evaluation questionnaire after completing the study of each program.Results: A total of 20 e-CME programs were developed and delivered to the learners and a total of 3644 learner-programs were studied. The cases rated the programs as 4.56 (SD=0.65) on a 1-5 Likert-type scale.Conclusions: Results showed that the learners rated this learning activity highly. However, we faced some challenges in developing the contents. In future, designing a comprehensive instructional system would help overcome these barriers.