Objective: To evaluate a vocational multidisciplinary rehabilitation programme for patients on long-term sick leave with respect to their work ability and return to work. Methods: A multidisciplinary rehabilitation programme was administered to an intervention group of 183 patients on long-term sick leave (mean 12.2 months). Effects of the treatment were compared with a control group (n = 96) recruited from the national sickness insurance record of patients on sick leave of 6–12 months duration (mean 11.5 months). Perceived work ability, return to work, background factors and psychosocial aspects of work were assessed on the basis of questionnaires at baseline and after 4 months. Results: Perceived work ability of the intervention group improved significantly after 4 months compared with the control group (p < 0.01). In the intervention group, 80% had returned to work compared with 66% in the control group (p = 0.06). Return to work after 4 months was predicted by good work ability at baseline, improved work motivation, improved work ability at follow-up and increased rumours of change in the workplace (R2 26.1–38.6%, p < 0.05). Conclusion: This multidisciplinary rehabilitation programme significantly improved perceived work ability compared with treatment as usual.