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We examined the impact of changes in the psychosocial work environment on depressive symptoms in a sample of junior physicians, a high risk group for stress and mental disorders.This is a three-wave prospective study in 417 junior physicians during their residency in German hospitals. The psychosocial work environment was measured by the Effort–Reward Imbalance (ERI) Questionnaire at Waves 1 and 2, and the depressive symptoms were assessed with the State-Trait Depression Scales at all three waves. Multivariate linear regression was applied for prospective associations between ERI across Waves 1 and 2, and baseline-adjusted depressive symptoms at Wave 3.Compared with the ERI scores at Wave 1, at Wave 2, and mean scores between the two waves, the baseline-adjusted ERI change scores between the two waves showed slightly better statistical power, predicting depressive symptoms at Wave 3 (β = 0.78, 95% CI = 0.38–1.18 for increased ERI per SD, β = 0.64, 95% CI = 0.22–1.06 for increased effort per SD, β = −0.65, 95% CI = −1.06 to −0.24 for increased reward per SD, and β = 0.68, 95% CI = 0.27–1.09 for increased overcommitment per SD).Negative changes in the psychosocial work environment, specifically increased ERI, are associated with depressive symptoms in German junior physicians. Reducing the non-reciprocity of working life, particularly improving reward at work, may have beneficial effects on prevention of mental health problems in the hospital workplace. Am. J. Ind. Med. 56:1414–1422, 2013. © 2013 Wiley Periodicals, Inc.