STUDY DESIGN: A cluster randomized controlled trial and economic evaluation with a 12-month follow-up and with work department as the unit of randomization. OBJECTIVE: To evaluate the effectiveness of a prevention program for low back pain (LBP) in an occupational setting with an economic evaluation. SUMMARY OF BACKGROUND DATA: LBP accounts for high economic costs in Western societies. Little is known on the effectiveness and related costs and savings of prevention programs for LBP. METHODS: The study population consisted of workers in physically demanding jobs from 9 large companies located throughout The Netherlands. In each company, 2 comparable work units were randomly allocated, resulting in 18 clusters with 258 workers assigned to the intervention group and 231 workers to the control group. RESULTS: Results in our study did not show significant differences in effects or costs savings of the program. Indirect costs related to work absence and productivity losses accounted for the majority (84%) of total costs due to LBP. CONCLUSIONS: This study provides no evidence for the adoption of this worksite prevention program for LBP.