OBJECTIVE: To evaluate the impact of instructional scaffolding on student performance and perceptions in a clinical debate activity within an infectious disease pharmacy elective course. METHODS: A sequential explanatory mixed-methods study was conducted from 2018 to 2022, involving pharmacy students enrolled in an infectious disease elective course. Students in the pre-scaffolding arm (2018) received traditional instruction, while those in the post-scaffolding arm (2019-2022) engaged in a scaffolded debate activity, comprising five milestone assignments and a mock debate. Student performance was assessed using group and individual debate rubrics. Student perceptions were evaluated through pre- and post-course surveys and thematic analysis of student reflections. RESULTS: Ninety-two students completed the elective (19 pre-scaffolding, 73 post-scaffolding). Group debate grades were higher in the post-scaffolding arm (median 94, interquartile range (IQR) [92,66] vs. 90 [90,91], p = 0.006), with no difference in individual debate grades. Students preferring debates/simulations had higher individual debate grades. Survey response rates were 100 % pre-course and 64 % post-course. Students in both arms reported increased confidence in defending clinical stances post-course, with higher confidence in the post-scaffolding arm. Qualitative results confirmed the debate activity as challenging, yet helpful in promoting communication, research, and professional skills. CONCLUSION: Scaffolding a clinical debate activity increased student grades, confidence, and communication skills. These findings suggest that scaffolding can effectively enhance educational outcomes in pharmacy education. Further research should explore optimal scaffolding tasks and methods of scaffolding support.