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To evaluate the cost-effectiveness of an activating guideline-based care (GBC) by occupational physicians (OPs).An economic evaluation was conducted in a randomized controlled trial with police workers on sick leave due to mental health problems (n = 240). In the intervention group trained OPs provided GBC, compared with usual care with easy access to a psychologist. Sick leave data and health care costs were gathered after 1-year follow-up. Analyses comprised bootstrap techniques, cost-effectiveness planes, and acceptability curves.Health care utilization costs (€574.532 in total) were significantly lower in the intervention group (mean difference −€520; 95% CI −€980 to €59), whereas there were no significant differences in days of sick leave and productivity loss costs.GBC could be cost-effective, as lower direct costs lead to equal treatment outcomes of workers with common mental disorders.