Teachers constantly strive to obtain reliable and appropriate teaching and assessment methods to maximize the learning experience. This study aimed to introduce combined modified team-based learning and open-book exams (TBL/OBEs) as learning and assessment strategies in clinical biochemistry for medical students and assess students' perceptions. Second-year medical students enrolled in the clinical biochemistry course were included in this study and subjected to TBL/OBE assessment. The assessment included two parts: the open-book format for half of the questions and the closed-book format for the other as a control. Upon completing the combined TBL/OBE session, the students were required to complete a structured survey to evaluate their perception of the experience. The data were gathered and analyzed. Data were presented as mean±standard error of the mean (SEM), and a p-value ≤0.05 was considered statistically significant. A total of 358 students completed the TBL/OBE and closed-book exam (CBE) and responded to the survey. Of these students, 76% preferred the OBE, and 84% thought it was a suitable learning method. On the one hand, the mean difficulty of the OBE format was 92.7±1.5 SEM, while, for the CBE, the mean difficulty was 88.7±1.9 SEM (p=0.015). On the other hand, the mean discrimination factor for OBE was 0.26±0.04 and, for the CBE, 0.41±0.04 SEM (p=0.0016). Males found the OBE questions easier (p=0.025) and less stressful (p=0.01). A combined model of modified TBL and OBE is a successful learning and assessment strategy in clinical biochemistry for medical students.