Objectives:To evaluate students’ perception towards the problem based learning (PBL) session in a system-based hybrid curriculum.Methods:We conducted a cross-sectional study in the College of Medicine, King Saud University, Saudi Arabia at the end of the 2012-2013 academic year. The survey questionnaire was self-administered, and examined perceptions of PBL session benefits, appropriate running of sessions, and tutor’s roles.Results:Out of 510 students, 275 (53.9%) completed the questionnaire. Most of the students reported that PBL sessions were helpful in understanding basic sciences concepts (p=0.04). In addition, they agreed that PBL sessions increased their knowledge of basic sciences (p=0.01). Most students reported that PBL sessions encouraged self-directed learning, collaborative learning, and improved decision making skills. However, 54.5% of students reported lack of proper training before starting the PBL sessions, and only 25.1% of students agreed that the teaching staff are well prepared to run the sessions. Most students used the internet (93.1%), lecture notes (76.7%), and books (64.4%) as learning resources. Most students reported repetition of topics between PBL sessions and lectures (p=0.07).Conclusion:The study highlighted the significant role of PBL in a system-based hybrid curriculum and helped students improve their knowledge and different learning skills. Students and staff training is required before the utilizing the PBL as an instructional method.