Background: Work related stress is an increasingly important occupational problem and a significant cause of economic loss. Objectives: To measure the prevalence and to determine the risk factors of work related stress among residents working in Ain Shams University Hospitals. Subjects and Methods: A cross-sectional study was conducted in which the study population consisted of residents working in different departments in the four main Ain Shams University Hospitals. In this study, 488 residents from a total of 557 accepted to participate, their age ranged from 24 to 29 years old (mean ± SD = 26.9 ± 1.3 years), 49.6% of them were males and 50.4% were females. Self- administered questionnaire was used including general health questionnaire-12 items (GHQ) and questionnaire for stress risk factors. Results: 58% of the residents were stressed, 28.1% of them scored mild stress and 29.9% scored severe stress. Regarding stress risk factors, being a female, difficulty in taking vacation, uncomfortable work environment, problems in communication with supervisors and perception of doing work of no value were the most important independent predictors for work related stress by using logistic regression model. Conclusion: Stress is prevalent among residents working at Ain Shams University Hospitals which imply that immediate intervention programs are needed to overcome these problems and to keep residents physically and mentally healthy.