Current guidelines recommend rehabilitative measures to alleviate dis- turbances resulting from cancer and its treatment. To give cancer survivors further assistance in getting back to work, work-related medical rehabilitation is currently being tested in Germany. In this cluster-randomized, multicenter trial, we studied the efficacy of work-related medical rehabilitation compared with conventional medical rehabilitation (trial no. DRKS00007770 in the German Clinical Trials Registry).A total of 484 cancer survivors of working age who were candidates for rehabilitation were recruited and assigned at random to either the intervention group (IG; work-related medical rehabilitation) or the control group (CG). The primary end- point was self-assessed function in a role one year after the end of rehabilitation, as evaluated with the health-related quality of life questionnaire of the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30). Further endpoints included symptom and function scales, subjective ability to work, coping with illness, and return to work. Neither the medical personnel nor the subjects were blinded.One year after the end of rehabilitation, data from 379 subjects who par- ticipated in the last follow-up survey were evaluated. The intervention and control groups did not differ significantly either in the primary endpoint of role function (IG = 60.8 vs. CG = 57.6 out of a maximum of 100 points; p = 0.204) or in any of the secondary endpoints. A last observation carried forward analysis yielded com- parable results. At 12 months, 28.5% of the subjects in the IG and 25.3% of those in the CG were still unable to work.This study did not reveal any significant clinically relevant advantage of work-related medical rehabilitation at one year. Future studies should determine whether a second period of rehabilitation might be helpful and whether selected subjects might benefit from the assistance of case managers beyond the period of rehabilitation.