Background: Empathy is an important component of overall clinical competence; thus, enhancing empathy in medical education is essential for quality patient care. Aim: This longitudinal study was designed to address the following questions: 1. Can a targeted educational program in communication skills training enhance empathy in medical students? and 2. Can such a program have a sustained effect? Methods: Study participants included 116 students who entered Okayama University Medical School in 2011. Students participated in a communication skills training program aimed to enhance their empathy, and completed the Jefferson Scale of Empathy (JSE) five times: at the beginning of medical school, prior to participation in the program, immediately after the program, and in last years of medical school. A total of 69 students, representing 59% of the cohort, completed the JSE in all five test administrations. Results: Students' total scores on the JSE and its two factors (Perspective Taking and Compassionate Care) increased significantly (p < 0.001) after participation in the communication skills training program. However, the program did not have a sustained effect. Conclusions: Targeted educational programs to enhance empathy in medical students can have a significant effect; however, additional reinforcements may be needed for a sustained effect. [ABSTRACT FROM AUTHOR]