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People on long-term sick leave often have a long-lasting process back to work, where the individuals may be in multiple and recurrent states; i.e., receiving different social security benefits or working, and over time they may shift between these states. The purpose of this study was to evaluate the effects of two vocational rehabilitation programs, compared to a control, on return-to-work (RTW) or increased employability in patients on long-term sick leave due to mental illness and/or chronic pain. In this randomized controlled study, 427 women and men were allocated to either (1) multidisciplinary team management, i.e., multidisciplinary assessments and individual rehabilitation management, (2) acceptance and commitment therapy (ACT), or (3) control. A positive outcome was defined as RTW or increased employability. The outcome was considered negative if the (part-time) wage was reduced or ceased, or if there was an indication of decreased employability. The outcome was measured one year after entry in the project and analyzed using binary and multinomial logistic regressions. Participants in the multidisciplinary team group reported having RTW odds ratio (OR) 3.31 (95% CI 1.39–7.87) compared to the control group in adjusted models. Participants in the ACT group reported having increased employability OR 3.22 (95% CI 1.13–9.15) compared to the control group in adjusted models. This study of vocational rehabilitation in mainly female patients on long-term sick leave due to mental illness and/or chronic pain suggests that multidisciplinary team assessments and individually adapted …