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Small group collaboration and knowledge construction plays an essential role in the outcomes of Problem-Based Learning (PBL). However, there is a dearth of systematic reviews that focus on knowledge construction during PBL in health professions education. To our knowledge, none of the few existing reviews have focused on the studies that directly analyzed the interaction process (versus only using indirect research methods). We conducted a systematic review of health professions education literature and identified 24 eligible empirical studies. Four major themes were identified: (1) interaction patterns, (2) types of knowledge, (3) language, linguistics, and culture, and (4) multimodalities/technology tools. We summarize the research methods, perspectives, analysis construct/measurements, and major findings of existing studies and discuss the implications for future research.