Introduction Work disability causes high costs for economy, organizations, and employees. However, medical rehabilitation does not always enable employees to return to their old jobs. In the present study, we investigated how disease classification and work characteristics interact in predicting the success of medical rehabilitation in terms of one’s ability to return to a former job. 
Methods To this end, we matched 2009 patient data from the German Statutory Pension Insurance agency with job characteristics data from the Occupational Information Network (O*NET) 17.0 database. We used a multilevel approach and a sample of N = 72,029, nested in 194 occupational groups. Results We found that workers are less likely to reenter a former job if mental illnesses coincide with emotionally demanding labor and if musculoskeletal diseases coincide with extreme environmental conditions. We did not find different effects between occupational groups for other types of diseases (circulatory system, neoplasms, injuries, others). 
Conclusion Thus, the contextual overlap of disease and occupational characteristics notably lowers the chances of a successful return-to-work. These findings should be taken into account by physicians when attempting to set realistic goals for rehabilitation in collaboration with the patient and the funding agency.