The rapid improvements in medical sciences and the ever-increasing related data, however, require novel methods of instruction. One such method, which has been given less than due attention in Iran, is problem-based learning (PBL). In this study, we aimed to evaluate the impact of study skills and the PBL methods on short and long-term retention of information provided for medical students in the course of respiratory physiology and compare it with traditional learning method. In this study, 39 medical students from Medical School of Kerman University of Medical Sciences, Kerman, Iran (2006-2010) were enrolled in the study and allocated randomly in three equal groups (13 in each group). All groups underwent a pre-test to be assessed for their basic information regarding respiratory physiology. Two groups were instructed using the traditional method, and one group used PBL. Among the two groups of the traditional method, one was instructed about study skills and the other was not. Once the PBL group took the study skill workshop, they were aided by tutors for their education. In the final term test, those students who had learned study skills and were instructed with the traditional method scored higher compared to other groups (p less than 0.05). However, in the 1 year (p less than 0.05) and 4 year (p less than 0.01) interval examinations, the PBL group achieved significantly higher scores. Despite the fact that PBL had no positive effect on the final term exam of our students, it yielded a more profound and retained understanding of the subject course. Moreover, considering the positive effect of study skills on long-term student scores, we recommend students to receive instructions regarding the appropriate study skills when initiated into universities.