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Background: Only a few studies of psychosocial determinants of employee health and organizational development have been prospective, involving more than one organization and applying standardized assessment tools. This limits the ability of providing evidence-based guidance as how to carry out healthy organizational transformations. Methods: A total of 6,000 employees responded twice to a validated psychosocial-leadership questionnaire within a 2-year period. The assessment focused on changes over time in the three outcome measures - mental health, efficacy, and leadership, determined to be important indicators of a healthy organization. Changes within and between organization were assessed statistically using regular t tests and general linear modeling. Results: There were major differences between organizations in psychosocial measures, both at the baseline and over time. At the organizational level, changes between study periods in management performance feedback, participatory management, and work tempo were the most consistent predictors of improvements over time in the three outcome measures. Conclusions: Performance feedback and participatory management might be two common predictors of healthy workplaces. Some of the psychosocial determinants of healthy organizations suggested in previous research might not be universally valid. It is suggested that future research should to a larger degree make use of multiple departments and organizations in studies of psychosocial determinants of healthy organizations.