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This nationwide cross-sectional study assessed the prevalence, possible risk factors, and impact of depression among Korean medical students.Of all medical students (14,095) registered in 41 medical schools in 2006 in South Korea, 7,357 (52.2%) completed the survey. Depression was measured using the patient-rated version of the Mini International Neuropsychiatric Interview (MINI-PR). Data on academic functioning, and sociodemographic characteristics were also obtained.Current, one-year, and lifetime prevalence of major depressive disorder (MDD) were 2.9%, 6.5%, and 10.3%, respectively. Possible risk factors for one-year MDD were female gender, lower class years, admission track with exemption from entrance exam, living alone at a lodging house or a rented room, and financial difficulty (P < .05). The grade point averages (GPAs) of students with MDD were significantly lower than those of nondepressed students for both semesters (t = 3.8, P < .001; t = 4.8, P < .001). The odds ratio of students with MDD of receiving a GPA below 2.0 was 1.8 (CI 1.4–2.4) as compared with nondepressed students.This study demonstrated that Korean medical students experience depression frequently. It also highlighted the possible risk factors of MDD among medical students and pervasive association of depression with poor functioning.