Aim and Background: University Students are at more risk for psychological problems. Although a lot of research in this area pointed out to situational risk factors of this phenomenon, but so far a comparative study between Iranian and non-Iranian has not been done. This study was done to compare the depression, anxiety, stress and quality of life in Iranian and non - Iranian students of the Medicine, Dentistry and Pharmaceutical schools of Isfahan University of Medical Sciences.Methods and Materials: This study conducted in a cross-sectional method on 1392 in Isfahan University of Medical Sciences. In this study, Depression Anxiety Stress Scale (DASS) used for assessing depression, anxiety and stress, and the short form of World Health Organization- Quality of Life (WHO-QOL-Bref) for quality of life assessment. After entering data into the computer, analysis was done using SPSS version 20 software and Fisher Exact tests, T test, Multivariate analysis, multiple regression and Pearson correlation statistical tests.Findings: The mean scores of anxiety, depression and stress in Iranian and foreign students was 28.88±20.11 and 38.47±33.57 respectively (p<0.001). Quality of life scores in the areas of physical health, psychological health, social relationships and environment were 24±4.1, 19.6±4.1, 9.8±2.2 and 26.2±4.8 respectively. Iranian students were significantly better than foreign students in the area of physical, mental, social health and environmental factor.Conclusions: Foreign students were different in depression, anxiety and quality of life scores with their Iranian counterparts represents that foreign students are more prone to experience psychological problems.