BackgroundThis study was conducted to explore the effectiveness of online problem-based learning (e-PBL) with multimedia animation scenarios by comparing the face-to-face (f2f) PBL method with paper-based scenarios. Adapting different f2f teaching methodologies to online environments is a significant problem that urgently needs attention, particularly in health education.MethodsThis study is part of design-based research and consists of three phases, which comprise design, analysis, and re-design. First, the animation-based problem scenarios were developed, and the learning environment (e-PBL) elements were organized. Then animation-based scenarios and the e-PBL environment were used, and problems related to the use of the environment were determined with an experimental study which was based on a pretest-posttest control group design. Finally, we used the following three measurement tools in the data collection process: a scale to determine the effectiveness of PBL, an attitude scale toward PBL, and the Clinical Objective Reasoning Exams (CORE). The study group in this research comprised 92 medical undergraduates (47 female and 45 male).ResultsThere were similar scores between the two groups (e-PBL and f2f) in terms of the effectiveness of the platforms, the attitudes of the medical undergraduates, and the CORE scores. Also, there were positive relationships between the attitude scores, grade point average (GPA), and PBL scores of the undergraduates. Another significant positive relationship was found between the CORE scores and the GPA.ConclusionsThe animation-supported e-PBL environment positively effects the participants’ knowledge, skills, and attitude. Students who have high academic scores attitude positively towards e-PBL. Providing problem scenarios as multimedia animations is the innovative face of the research. They have been produced inexpensively with off-the-shelf web-based animation apps. These technological advances may democratize the production of video-based cases in the future. Although the results of this study were obtained before the pandemic, they showed no differences between e-PBL and f2f-PBL in terms of effectiveness.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12909-023-04298-x.