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Abstract Background This study aimed to investigate the impact of interactive lecture (IL) and team-based learning (TBL) on improving clinical reasoning skills (CRSs) and achieving learning outcomes (LO). Students’ feedback was obtained about the strategies. Methods This study was carried out at the Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia. Two modules, endocrinology, and emergency were selected. Students of each batch in both modules were divided into two arms. With a randomized crossover design, IL & TBL were used for two separate topics in each module. After each topic, a quiz in the form of well-structured MCQs was taken. A questionnaire was designed to obtain students’ feedback. SPSS version 23 was used to analyse results. The difference between the mean values was calculated by Student’s t-test. Feedback data is presented as frequency. P-value ≤ 0.05 was considered statistically significant. Results Learning outcomes were achieved by all groups in two modules, with both instructional strategies, IL and TBL. Students attempted >70% correct answers. However, in the emergency module, the groups with TBL as the instructional strategy performed better in quiz1 and quiz 2 (p = 0.026 and p = 0.016, respectively). Similarly, in the endocrinology module (3rd year), although the groups with TBL as the instructional strategy performed better in both quizzes, it was significant in quiz1 (p = 0.02). The difficulty indices of the clinical reasoning questions (CRQ) were used as the parameters for comparison. In the emergency module, group1, in quiz1, with TBL as an instructional strategy performed better in the CRQ (p = 0.017), while in quiz2, group2 with TBL as the instructional strategy performed better (p |