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The purpose of this study is to develop a conceptual framework to explain the role of group discussion in problem-based learning (PBL) to enhance medical students’ hypothetico-deductive reasoning skills. The conceptual framework integrates the notions of hypothetico-deductive reasoning, PBL, and discussion in a way that explains the specific role of group discussion in enhancing students’ hypothetico-deductive reasoning during PBL. Recommendations for new PBL strategies and implications for future PBL research directions will be discussed.