With the introduction of integrated approach in the medical curriculum, there is a need to teach basic sciences in a way relevant to real clinical scenarios. The aim of this study is to investigate the feasibility of case-based learning (CBL) for teaching of medical biochemistry to a large number of medical students. It also evaluates both the students’ and faculty members’ perception of this approach. CBL was introduced in teaching medical biochemistry in the Neuroscience block for the second-year medical students. This study’s students were from two consecutive academic years (n = 721 and 769). Four clinical cases were prepared. Students were divided into subgroups, each having one CBL session every 2 weeks. Students were encouraged to work together to understand the given clinical scenario by building on past knowledge obtained through other teaching modalities and new knowledge acquired during the session. A pretest was administered at the beginning of the session, and an identical posttest administered at the end of the session. Perception of both the students and facilitators of the CBL-teaching approach was evaluated using end-of-block questionnaires. In both studied academic years, students got higher scores in posttest compared to pretest scores with a statistically significant difference of the paired scores (P < 0.001). Analysis of the students’ questionnaire demonstrated that most students positively perceived the CBL approach, with a feeling that CBL has helped them learning the biochemistry concepts. Likewise, analyzing staff questionnaire revealed staff’s positive attitude toward the impact of CBL in teaching biochemistry on the students and on themselves. The current work suggests that CBL is both feasible and efficient to be applied for teaching medical biochemistry on a large scale. It is positively perceived by both students and teaching staff. Future work is still needed to solve certain challenges such as increasing work load on the faculty members and to test the impact of this teaching modality on long-term retention of knowledge.