Background: To prolong sustainable healthy working lives of construction workers, a prevention program was developed which aimed to improve the health and work ability of construction workers. The objective of this study was to analyze the cost-effectiveness and financial return from the employers' perspective of this program. Methods: A total of 293 workers in 15 departments were randomized to the intervention (n=8 departments) or control group (n=7). Data on work ability and health were collected using questionnaires. Sick leave data were obtained from the companies. Both the cost-effectiveness analyses and return on investment analyses were performed. Results: After 12 months, the absenteeism costs were significantly lower in the intervention group than in the control group. At 12-month follow-up, no significant differences were found with respect to the primary outcomes (work ability, mental and physical health status) and secondary outcomes (musculoskeletal symptoms), meaning that the intervention was not cost-effective in comparison with the control group. The net-benefit was €641 per worker, and the intervention generated a positive financial return to the employer. Conclusion: The intervention in the present study was cost-saving to the employer due to reduced sickness absenteeism costs in the intervention group compared with the control group. However, the intervention cannot be regarded as cost-effective as no significant effects were found for work ability and health. Am. J. Ind. Med. 57:56-68, 2014. © 2013 Wiley Periodicals, Inc.