Objectives: Medical students may experience stressful condition due to their curriculum burden and career responsibilities. Adverse physical and mental health leads to impaired quality of life of medical students which may affect their learning and academic capabilities during medical education. Aim of the study: The purpose of this study was to assess the quality of life-based on WHO-QOL-BREF protocol among medical students studying in Riyadh, Saudi Arabia. Methods: A cross-sectional study was conducted among medical students at the College of Medicine, Al-Imam Muhammad Ibn Saud Islamic University, Riyadh during the year 2014. The data for quality of life was collected by a well-designed questionnaire as prescribed by the WHO-QOL-BREF which includes questions pertaining to different domains for the quality of life. Results: Total 983 male medical students from different academic year participated in this study, who voluntarily filled their questionnaires for quality of life. The overall Cronbach’s a coefficient of the WHO-QOL-BREF questionnaire was 0.837. Students staying with family had a higher overall QOL score than those living alone (p<0.05). The scores according to different academic years were significantly different in the environmental health domain (p<0.05); in which second-year students had the least score and fifth-year students had the highest score. Conclusion: In this study, we found that the medical students were found to have a decreased quality of life. Students who lived with family led to an improvement in the quality of life in some domains. There is a need for psychological support for students living alone and those in the middle of their medical course.