The aim of this study was to analyse the impact of the effort–reward imbalance (ERI) model on intent to leave the current organization (ITL organization) and intent to leave the nursing profession (ITL profession) in a prospective way. A total of 1,531 health care workers who remained in their job filled in a self-administered questionnaire at baseline and 1 year later. ERI was measured at baseline by a 23-item questionnaire. Multivariate logistic regression analyses were performed. Within a population with low intent to leave at baseline, we found that an imbalance between high efforts and low rewards (extrinsic hypothesis) increased the risk of high ITL organization (OR 4.98; 95% CI 2.07–11.97) and high ITL profession (OR 1.84; 95% CI 1.03–3.30), 1 year later. A high level of overcommitment (OC; intrinsic hypothesis) was not predictive for both intent to leave outcome variables, neither was the interaction between high efforts/low rewards and a high level of OC (interaction hypothesis). Our results showed that a perceived effort-reward imbalance (ERI) at work is a significant predictor of intent to leave among health care workers. This contribution concludes with some directions aimed at boosting nurses’ retention and recommendations for future research.