Background: To evaluate the efficacy of a multidisciplinary vocational programme in sick-listed, primary health care patients as compared to matched non-programme patients. Methods: The design was a 3-year prospective population-based, matched case-control study. It was set in a large primary healthcare centre in the city of Eskilstuna, Sweden. The subjects were 943 sickness-certified patients (482 women and 461 men). 170 high-risk patients and a matched control group (n = 340) with similar risk for not returning to work within expected time, based on propensity score was created. The intervention group passed a multidisciplinary medical assessment and a coordinated vocational programme, while the control group received usual care by their general practitioner. Main outcome was sick leave conclusion and the day when it occurred. Results: The follow-up time was subdivided into four periods. During the first two periods, days 1-14 and days 15-112 after baseline, the intervention group had a significantly lower sick leave conclusion rate than the control group (hazard ratios, (HR) 0.32, 95% CI 0.20-0.51, p < 0.0001 and 0.47, 95% CI 0.35-0.64). During the third period, days 113-365, the intervention group had an insignificantly lower conclusion rate (HR 0.70, 95% CI 0.46-1.08, p = 0.10), and during the fourth follow-up period, days 366-1096, the intervention group had an insignificantly higher conclusion rate than the control group (HR 1.16, 95% CI 0.69-1.96, p = 0.58). Across the total follow-up period, the intervention group had a lower conclusion rate than the control group (HR 0.55, 95% CI 0.45-0.66, p < 0.0001). Conclusions: No positive significant effects of the rehabilitation programme on time to sick leave conclusion were found.