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Abstract Background Implementing PBL in teaching and learning can be challenging due to a variety of complex barriers. Studies on barriers to the implementation of problem-based learning in Ethiopia are scarce. This study aimed to explore the barriers to the implementation of problem-based learning at the Debre Berhan University Medical School. Methods A qualitative study was conducted among faculty and medical students at the medical school. Purposive sampling was used to select participants. Semi-structured interviews were conducted with tutors and academic leaders, including the problem-based learning coordinator, the biomedical sciences coordinator, and the school dean. Data was also collected from students through focus group discussions. All interviews and discussions were recorded. The four steps of data analysis of Spradley, including domain analysis, taxonomic analysis, componential analysis, and theme analysis, were employed. Results The study identified student-related, tutor-related, case scenario-related, and assessment-related barriers as the most significant obstacles to implementing problem-based learning. These barriers included work overload for both students and tutors, lack of training and experience among tutors, student reluctance, absence of standardized case scenarios, subjectivity of assessment methods, and on-the-spot assessment of students. Conclusions and recommendations : Lack of both tutor and student commitment, lack of standardized cases, absence of a recognition of staff input, gap in communication skills, work overload, lack of continuous training, and at-spot evaluation of students were identified as the main barriers to the implementation of PBL.