Problem-based learning (PBL) can be described as a learning environment where the problem drives the learning. This technique usually involves learning in small groups, which are supervised by tutors. It is becoming evident that PBL in a small-group setting has a robust positive effect on student learning and skills, including better problem-solving skills and an increase in overall motivation. However, very little research has been done on the educational benefits of PBL in a large classroom setting. Here, we describe a PBL approach (using tutorless groups) that was introduced as a supplement to standard didactic lectures in University of British Columbia Okanagan undergraduate biochemistry classes consisting of 45-85 students. PBL was chosen as an effective method to assist students in learning biochemical and physiological processes. By monitoring student attendance and using informal and formal surveys, we demonstrated that PBL has a significant positive impact on student motivation to attend and participate in the course work. Student responses indicated that PBL is superior to traditional lecture format with regard to the understanding of course content and retention of information. We also demonstrated that student problem-solving skills are significantly improved, but additional controlled studies are needed to determine how much PBL exercises contribute to this improvement. These preliminary data indicated several positive outcomes of using PBL in a large classroom setting, although further studies aimed at assessing student learning are needed to further justify implementation of this technique in courses delivered to large undergraduate classes.