Objectives: This longitudinal study aimed to test the hypothesis that organizational work factors (OWFs) may be related to depressive symptoms through an increased effort-reward imbalance (ERI) ratio among registered nurses (RNs) and nursing assistants working in hospitals. Methods:We studied 2117 female RNs and nursing assistants who stayed in the same work unit and position during the follow-up from the ORSOSA (ORganisation des SOins-SAnt'e) longitudinal study. The work characteristics and workers' health were assessed in 2006 and 2008. Results: We confirmed our hypothesis of both direct and mediated effects of OWFs on workers' health. We showed that issues about patient-related information exchanges increased RNs' depressive disorders by increasing first a perceived ERI. Conclusions: Our results advocate integrating both the work organizational level and the individual level into preventive actions to improve workers' mental health.