Background:There are very few evaluations of the effectiveness of leadership development programs. The purpose of the study was to examine whether an art-based leadership program may have a more beneficial effect than a conventional one on leaders' and their corresponding subordinates' mental and biological stress. Methods: Participating leaders were randomized to 2 year-long leadership programs, 1 art-based and 1 conventional, with follow-up of the leaders and their subordinates at 12 and 18 months. The art-based program built on an experimental theatre form, a collage of literary text and music, followed by writing and discussions focused on existential and ethical problems. Results: After 18 months a pattern was clearly visible with advantage for the art-based group. In the art group (leaders and their subordinates together as well as for subordinates only) compared to the conventional group, there was a significant improvement of mental health, covert coping and performance-based self-esteem as well as significantly less winter/fall deterioration in the serum concentration of the regenerative/anabolic hormone dehydroepiandrosterone-sulfate. Conclusions: Our findings indicate a more beneficial long-term health effect of the art-based intervention compared to a conventional approach. Positive results for both standardized questionnaires and biological parameters strengthened the findings. The study provides a rationale for further evaluation of the effectiveness of this alternative educational approach.