Objectives: Since 2014, the Federal German Pension Insurance has approved several departments to implement work-related medical rehabilitation programmes across Germany. Our cohort study was launched to assess the effects of work-related medical rehabilitation under real-life conditions. Methods: Participants received either a common or a work-related medical rehabilitation programme. Propensity score matching was used to identify controls that were comparable to work-related medical rehabilitation patients. The effects were assessed by patient-reported outcome measures 10 months after completing the rehabilitation programme. Results: We compared 641 patients who were treated in work-related medical rehabilitation with 641 matched controls. Only half of the treated patients had high initial work disability risk scores and were intended to be reached by the new programmes. The dose of work-related components was on average in accordance with the guideline; however, the heterogeneity was high. Work-related medical rehabilitation increased the proportion of patients returning to work by 5.8 percentage points (95% CI 0.05 to 0.11), decreased the median time to return to work by 9.46 days (95% CI -18.14 to -0.79), and improved self-rated work ability by 0.38 points (95% CI 0.05 to 0.72) compared with common medical rehabilitation. A per-protocol analysis revealed that work-related medical rehabilitation was more effective if patients were assigned according to the guideline and the minimal mandatory treatment dose was actually delivered. Conclusions: The implementation of work-related medical rehabilitation in German rehabilitation centres affected work participation outcomes. Improving guideline fidelity (reach and dose delivered) will probably improve the outcomes in real-world care.