Background: Medical education in the last two decades has shifted from teacher-centered methods to studentcentered methods, where students are learning through active participation. Clinical case-based learning (CBL) was found to be one of the excellent approaches to promote students learning. It enhances their critical thinking, problem-solving ability, knowledge retention, and exam preparation. The objective of the current study was to assess students’ perception on the usefulness of CBL approach in Microbiology and Immunology course. Methodology: This study was conducted at College of Medicine and Health Sciences among 5th-year medical students of 2017- 2018 batch. The study design included pretest, CBL discussion on selected topics, and the posttest after the CBL session. The data were collected, tabulated, and statistically analyzed using Microsoft Excel and SPSS version 22. The student’s “t” test was used to compare pretest and posttest results and the p<0.05 was considered as statistically significant. Results: A total of 114 fifth year medical students participated in the study. Majority of the students were in favor of CBL activity. More than 85% of the students stated that they enjoyed the activity and about 80% indicated CBL activity improved their critical thinking, problem-solving skills, and clinical reasoning. Majority of the students (90.35%) said it improved their knowledge retention and about 64.04% stated that it improved their exam grades. The difference between pretest and posttest scores was statistically significant with p<0.05. Conclusion: CBL is an excellent educational tool to motivate and promote students learning. It enhances students’ analytical thinking, clinical reasoning, conceptualization, and knowledge retention. It also benefits students in terms of their better examination preparation and performance.