Objectives: To determine the frequency of depression among post graduate medical trainees in a teaching hospital of Pakistan and to explore the associated factors contributing to depression in them. Methods: It's a cross-sectional study at the Aga Khan University Hospital, Karachi. It was done in June 2008 till August 2008. Zung Self-Rating Depression Scale was administered among 172 post graduate trainees. Self administered questionnaires were used to assess the associated demographic and work related risk factors. Adjusted odds ratios (OR) were calculated by logistic regression. Results: The survey response rate was 172(82.69%). Depression in the overall sample was 103(59.88%), of which 58(33.66%) were moderate to markedly depressed. Multiple logistic regression analysis revealed that working hours less than 76 hours (OR 3.71; CI=1.67, 8.23) and 76-90 hours (OR 3.15; CI= 1.42, 6.97) and none or occasional peer support (OR 2.05; CI=1.01, 4.18) were independent predictors for depression among the post graduate trainees. Conclusion: More than half of our sample population was depressed. Therefore, they should be encouraged to recognize and seek treatment. This study also indicates that less working hours and lack of peer support cause depression.