Objective: The study aims were to investigate whether mindfulness predicts improved work ability after a multifactorial vocational rehabilitation program in Norway and to examine the mediating influence of mindfulness in the relationship between personal health factors and changes in work ability in response to the program. Methods: Seventy-four participants on long-term sick leave completed questionnaires assessing mindfulness, work ability, functional health, psychological functioning, and demographics before and after a 4-6-week multidisciplinary vocational rehabilitation program. In addition to a standard logistic regression analysis, a bias-corrected bootstrapping technique was used to test the hypothesized indirect effects. Results: Enhanced mindfulness over the course of the program significantly predicted a positive change in work ability. Furthermore, decreased personal burnout and enhanced selfesteem were both unique predictors of such positive change. Mindfulness mediated the effects of personal burnout and selfesteem on participants' work ability. Increased body responsiveness and sense of mastery, and decreased pain consequences and subjective health complaints, were indirectly related to positive changes in work ability through increased mindfulness. Conclusion: Enhancing mindfulness skills is useful for improving the work ability of Norwegians on long-term sick leave.