Background: In medical practice, a relationship of trust between doctors and patients is essential. An important part of building and maintaining this relationship is empathy. Prior studies have suggested that empathy in medical students declined around the fourth year. The purpose of this study is to verify the decrease of empathy and gain further insights into empathy factors. Methods: This longitudinal study of undergraduate medical students was conducted through a self-administered, 20-item survey, using a 5-point Likert scale. First (n=105) and fourth (n=62) year students at Yamagata University Faculty of Medicine, School of Medicine in Japan were assessed for empathy using the Japanese version of the Jefferson Scale of Physician Empathy (JSPE). Total empathy scores were calculated, and multivariate analysis of variance (MANOVA) was used to reveal the underlying factors of the Japanese version of JSPE. Finally, logistic regression analysis was used to investigate the presence of any relationships between attributes such as gender-related differences, age, school year, and experience as a patient. Results: In total, 234 participants were contacted, of whom 167 responded (71.3%). No decrease of mean empathy scores was shown between first-year (66.4) and fourth-year students (68.4). Factor analysis identified four factors: “building good patient-doctor relationship,” “importance of empathetic care,” “understanding patients’ view,” and “compassionate care.” A weak correlation (r = - 0.271) was observed between “understanding patients’ view” and “importance of empathetic care.” The odds ratio of females in “understanding patients’ view” and “compassionate care” was significantly higher (p<0.05) than in males. For “compassionate care,” statistically significant differences were noted for gender (p < 0.05) and age (p< 0.05) and the effect of gender being larger than age. Conclusions: This longitudinal cohort study in one medical school in Japan showed that empathy scores of first- and fourth-year students did not decrease, and the contribution of “compassionate care” was lowest of the four factors. The results imply the necessity to provide a program that enables preclinical medical students to understand the significance of emotional empathy and express it before they appear for computer-based testing (CBT) and objective structured clinical examination (OBCE) in their fourth year.