Objective: To estimate the prevalence of depression and anxiety symptoms and identify the associated risk factors in first and fifth year medical students at the University of Medicine and Pharmacy in Ho Chi Minh City. Methods: A cross-sectional study was carried out on medical students at the University of Medicine and Pharmacy in Ho Chi Minh City, Vietnam, from April to June 2012. A questionnaire was administered to 220 students (110 first year students and 110 fifth year students). The PHQ-9 (Patient Health Questionnaire 9) was used to screen for depression, and the Generalized Anxiety Disorder 7-item scale (GAD-7) was used to screen for generalized anxiety disorder. Additional questions concerning socioeconomic data were also included in a self-report survey. Results: 213 out of the 220 students surveyed satisfied the study criteria and were therefore included in the study. The prevalence of depression and anxiety were 27.2% and 10.3% respectively. 25.9% of first year students and 28.6% of fifth year students were depressed. Meanwhile, 10.2% of first year students and 10.5% of fifth year students had high levels of anxiety. The data further revealed that students’ living conditions, family support, level of satisfaction with their academic program and university facilities, and certain characteristics (specifically their desire to study medicine and their propensity to share their difficulties) were significantly associated with both depression and anxiety. Conclusions: This study suggests that medical students in Vietnam have higher prevalence of depression and anxiety than the general population and that certain risk factors predispose medical students to anxiety and depression.