Background: Medical teaching requires innovative methods through which teachers can provide a student-centered learning environment that improves students' learning through their active participation. The patient-oriented problem-solving (POPS) system is an active learning tool that permits students to work in small groups to solve clinical problem, promotes self-learning, enhances clinical reasoning, and enriches their knowledge, and long-term memory. The aim of the study was to implement POPS session in immunology course and assess the students' perception of the effectiveness of POPS teaching in learning immunology. Methodology: 121 students were divided into small groups of 10 each. The pre-test questions were given to assess their previous knowledge before the POPS activity. Post-test questions were given after the activity to check the effectiveness of POPS session in learning. A questionnaire was also given at the end of the activity to assess the students' perception of POPS activity in learning. The data were collected, tabulated, and statistically analyzed. Results: Significant improvement in the mean differences between pre-and post-test scores of the students, suggests the effectiveness of POPS teaching activity. A majority of the students (>80%) stated that POPS promotes self-learning, creates interest, enhances conceptualization, empowers critical thinking, and problem-solving skills. Conclusion: POPS activity is a good educational method to enhance the learning skills of the medical students.