Objectives. To establish an aggressive problem- based learning (PBL) format for the medicinal chemistry course and assess the outcomes of student learning. Methods. To assess learning in the new format, precourse and postcourse examinations were given to students enrolled before and after problem- based learning was implemented, and appropriate statistical analyses were conducted. Results. The PBL cohort did not learn the same amount of factual content yet performed the same on higher-order thought questions as the non-PBL cohort. Conclusions. Problem-based learning may not be the ideal method for teaching medicinal chemistry. This may be due to several factors including: student learning type, the lack of a cognitive framework for learning in the basic sciences, and time constraints.