The effort-reward imbalance is an important psychosocial factor which is related to poor health among employees. However, there are few studies that have evaluated effort-reward imbalance among medical residents. The present study was done to determine the association between psychosocial factors at work as defined by the effort-reward imbalance model and depression among Japanese medical residents. We distributed a questionnaire to 227 medical residents at 16 teaching hospitals in Japan at the end of August 2005. We asked participants to answer questions which included demographic information, depressive symptoms, effort-reward imbalance, over-commitment and social support. Depression was evaluated using the Japanese version of the Center for Epidemiologic Studies-Depression (CES-D) scale. The effort-reward imbalance and over-commitment were assessed by the Effort-Reward Imbalance (ERI) questionnaire which Siegrist developed. Social support was determined on a visual analog scale. Logistic regression analysis was performed to determine the associations between effort-reward imbalance and depressive symptoms. Depressive symptoms were found in 35 (29.2%) 1st-year residents and 21 (27.6%) 2nd-year residents. The effort-reward ratio >1 (OR, 8.83; 95% CI, 2.87-27.12) and low social support score (OR, 2.77, 95% CI, 1.36-5.64) were associated with depressive symptoms among medical residents. Effort-reward imbalance was independently related to depression among Japanese medical residents. The present study suggests that balancing between effort and reward at work is important for medical residents' mental health.