Psychosocial factors at work have been found to be significant contributors to health, especially cardiovascular health. This study is aimed at exploring the relationship between psychosocial factors at work as defined by the effort-reward imbalance (ERI) model and self-reported health, using alternative formulations of this model, and comparing cross-sectional and prospective analyses for a large occupational cohort of men and women. The French version of the ERI model was used to measure the three scales of effort, reward, and overcommitment. Self-reported health was used as health outcome. Covariates included chronic diseases, frequent depressive symptoms, and personal, occupational, and behavioural factors. The cross-sectional and prospective analyses concerned, respectively, 10175 and 6286 workers. Men and women were analysed separately. Cross-sectional analysis revealed that ERI was significantly associated with self-reported health whatever the formulation used (ratio over one, quartiles, continuous ratio, or log-transformed ratio) for both genders. When effort and reward were studied as two separate variables, reward was a significant risk factor for both genders, whereas effort was for men only. Overcommitment was also found to be a risk factor for self-reported health for both sex. Prospective analysis showed that ERI was a significant predictor of poor self-reported health for men and women for two formulations (continuous ratio and log-transformed ratio). For both genders, effort did not predict self-reported health, but reward did. Overcommitment was predictive of poor self-reported health for men only. Our results highlighted the predictive effects of the ERI model on self-reported health in a 1-year follow-up study. They urged to explore various formulations of the ERI model. They also underlined the need for longitudinal study design and separate analyses for men and women in the field of psychosocial factors at work.