Background In Indonesia, the prevalence of mental health issue with depressive and anxiety symptoms in teenagers above 15 years old reach approximately 6% of the total population. Medical school can cause a significant psychological pressure to medical students. Anxiety and depression scale are increasing in no time, showing a stressor in the curriculum and environment. Aim This research is needed to analyze some risk factors of anxiety and depression in medical students of UPH. There are five factors that would be studied in this research, such as genders, study course length, self-esteem, self satisfaction towards achievement, and social support. Material & Methods A cross-sectional study was conducted among students of UPH Faculty of Medicine. The samples consisted of 270 pre-clinical medical students of UPH. -Esteem Scale (RSES) and Multidimensional Scale of Perceived Social Support (MSPSS) were used in the research, as well as a questionnaire on personal information which included data on course of study and personal satisfaction regarding their GPA. Data were analyzed with SPSS using chi-square and logistic regression. Result The results of this study showed that 66% of the examined student population had symptoms of anxiety and 40% had symptoms of depression, varying from moderately to extremely showing. Self esteem (p < 0.001, OR 3.75, (95% CI, 2.05 - 6.87)) and personal satisfaction towards achievement (p < 0.001, OR 9.88, (95% CI, 4.99 - 19.57)) are positively associated to anxiety. Course of study (p < 0.001, OR 0.27, (95% CI, 0.14 - 0.2)), self-esteem (p < 0.001, OR 3.53, (95% CI, 2.02 - 6.15)), and social support (p < 0.001, OR 3.02, (95% CI, 1.75 5.21)) are positively associated to depression. Other variables studied in this research show no significant relation to either anxiety or depression. Conclusion Low self-esteem and dissatisfaction towards achievement are the risk factors of anxiety while course of study below 3 years, low self-esteem and low social support are the risk factors of depression in medical students of UPH.