The objective of this study is to compare the costs and benefits of a graded activity (GA) intervention to usual care (UC) for sick-listed workers with non-specific low back pain (LBP). The study is a single-blind, randomized controlled trial with 3-year follow-up. A total of 134 (126 men and 8 women) predominantly blue-collar workers, sick-listed due to LBP were recruited and randomly assigned to either GA (N = 67; mean age 39 ± 9 years) or to UC (N = 67; mean age 37 ± 8 years). The main outcome measures were the costs of health care utilization during the first follow-up year and the costs of productivity loss during the second and the third follow-up year. At the end of the first follow-up year an average investment for the GA intervention of €475 per worker, only €83 more than health care utilization costs in UC group, yielded an average savings of at least €999 (95% CI: −1,073; 3,115) due to a reduction in productivity loss. The potential cumulative savings were an average of €1,661 (95% CI: −4,154; 6,913) per worker over a 3-year follow-up period. It may be concluded that the GA intervention for non-specific LBP is a cost-beneficial return-to-work intervention.