Sickness absenteeism caused by musculoskeletal disorders (MSDs) is a persistent and costly occupational health challenge. In a prospective controlled trial, we compared the effects on sickness absenteeism of a more proactive role for insurance case managers as well as workplace ergonomic interventions with that of traditional case management. Patients with physician-diagnosed MSDs were randomized either to the intervention group or the reference group offered the traditional case management routines. Participants filled out a comprehensive questionnaire at the initiation of the study and after 6 months. In addition, administrative data were collected at 0.6, and 12 months after the initiation of the project. For the entire 12-month period, the total mean number of sick days for the intervention group was 144.9 (SEM 11.8) days/person as compared to 197.9 (14.0) days in the reference group (P < 0.01). Compared with the reference group, employees in the intervention group significantly more often received a complete rehabilitation investigation (84% versus 27%). The time for doing this was reduced by half (59.4 (5.2) days versus 126.8 (19.2), P < .01). The odds ratio for returning to work in the intervention group was 2.5 (95% confidence interval 1.2-5.1) as compared with the reference group. The direct cost savings were USD 1195 per case, yielding a direct benefit-to-cost ratio of 6.8. It is suggested that the management of MSDs should to a greater degree focus on early return to work and building on functional capacity and employee ability. Allowing the case managers a more active role as well as involving an ergonomist in workplace adaptation meetings might also be beneficial.