The cost effectiveness of work-oriented rehabilitation for persons on long-term sick leave needs to be assessed. This prospective observational study presents a follow-up seven years after rehabilitation using two different evidence-based work-oriented regimens. Individuals on sick leave for neck and back pain were referred to two rehabilitation programmes in Sweden. The first programme was a relatively low-intensity programme based on orthopaedic manual therapy and exercise programme (OMTP). The second programme was a full-time multidisciplinary programme (MDP). The primary outcome was sickness absence seven years after intervention. Cost effectiveness was calculated on the basis of loss of production due to sickness absence. The results show that participants referred to MDP and with less than 60 sick days before rehabilitation have reduced sickness absence after intervention as compared to matched controls. This corresponds to a cost reduction of about 94,494 EUR per referred individual. Further, the results indicate that participants of the OMTP who have more than 60 sick days before rehabilitation have a statistically significant increased risk of disability pension. This means increased cost in terms of loss of production of 44,593 EUR per referred individual. The results of this study show that MPD but not OMTP achieves the goal of working life-oriented rehabilitation. A direct comparison between the rehabilitation programmes strengthened the assumption that long-term sickness absence prior to rehabilitation is associated with more days on sick leave after rehabilitation. This analysis also indicated the importance of participants' pain self-efficacy beliefs and recovery beliefs on rehabilitation outcome.