Purpose Vocational rehabilitation (VR) is a widely used intervention aimed to optimize work participation for patients on sick leave due to chronic musculoskeletal pain (CMP). Economic evaluations of care as usual VR are scarce, and may provide relevant information to guide clinical, reimbursement and policy decisions. The aim of this study was to evaluate the short-term cost-effectiveness and return on investment (ROI) of VR for patients on sick leave due to CMP with an additional work module (VR+) compared to VR without work module, from a societal and employers' perspective. Methods A retrospective longitudinal cohort study within a Dutch care as usual context was applied. Participants with CMP and decreased work participation originating from seven Dutch rehabilitation centers were included in this study. Participants underwent VR or VR+. Main data sources at baseline and discharge: Quality-adjusted life year (QALY) based on EQ-5D, intervention costs, self-reported productivity and health care utilization. Main analyses cost-effectiveness, including incremental cost-effectiveness ratio (ICER) and a cost-effectiveness acceptability curve (CEAC); and ROI analyses with use of the human capital method. Results N = 324 participants were analyzed. The results show that VR+ was cost-effective compared to VR: mean cost savings of €820 per 0.012 QALY gained. CEAC suggests probability of VR+ being cost-effective is > 0.91 for thresholds of €20.000 and higher. The mean ROI of VR+ for employers was 38%. Conclusion It was concluded that at discharge, VR+ was cost-effective compared to VR. ROI was positive for employers.