This study determines whether dispositional optimism moderates the relationship between role conflict and the risk of disability retirement. The study was based on a combination of self-report survey questionnaire data on role conflict and dispositional optimism with official register data on disability benefits from the Norwegian Labour and Welfare Administration. The sample comprised 14,501 Norwegian employees from various occupations and industries. Role conflict was significantly related to higher risk (HR 1.35, 95% CI 1.19–1.53), whereas optimism was associated with decreased risk (HR 0.75, 95% CI 0.64–0.88), of disability retirement. Optimism did not modify the effect on role conflict on disability retirement. Having an optimistic life orientation decreases the risk of disability retirement in general, but does not protect against the detrimental effects of role conflict at the workplace. As optimism is a malleable personality characteristic, organizations may benefit from interventions that help employees experience daily events more positively.