Introduction: Case-based learning (CBL) promotes integration of knowledge and practice. During CBL, students are exposed to the real medical problems. The present study was conducted to introduce CBL as a teaching/learning (T/L) tool in the Department of Biochemistry and to determine its effectiveness in enhancing students’ knowledge and also to make the students aware of relevance of biochemistry in clinical settings. Materials and methods: After permission from Ethical Committee, both faculty and students were sensitized to CBL; questionnaires and feedback pro forma for students and faculty were finalized. Total of 126 students of first-year Bachelor of Medicine and Bachelor of Surgery (MBBS) were included in the study, and they were divided into two groups. Both groups I and II comprised 63 students each. The study group I (n = 63) was given a clinical problem with specific learning objectives 2 days before CBL session. Pretest questionnaire was administered to both the groups. Group I underwent a CBL session and group II had the same teacher teaching the topic in a didactic lecture form. Both the groups were given a posttest. Crossover of groups was done for the second clinical case. Structured feedback questionnaire on acceptability and usefulness of this method was taken from both the students and the faculty. Using Student's paired and unpaired t-test, the results of pretest and posttest were analyzed. Results: The majority of students (89%) agreed that CBL form of teaching was better than didactic lectures in understanding the topic. For clinical application of knowledge of biochemistry, 85% of the faculty agreed that CBL was a better T/L tool. Conclusion: Among medical students, CBL is effective for better understanding of biochemistry. It motivates students to become self-directed learners. Along with didactic lectures it should be a part of teaching curriculum.