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To be viewed as successful, corporate health promotion and disease prevention programs must demonstrate that they can improve the risk profile of employees as a whole, and, in particular, those employees at highest risk. This study reports the effectiveness of Johnson & Johnson’s newly configured Health & Wellness Program in reducing the health risks of 4586 employees who participated in two serial health screening programs, with a minimum of 1 year between screenings. The study also examines the impact of participation in a high-risk intervention program called Pathways to Change® on health risk factors. McNemar chi-squared and z-test statistics were used to evaluate changes in health risks over time. Results indicate significant risk reduction in 8 of 13 risk categories examined for all employees who participated in two health risk assessments over an average of 23/4 years. When comparing Pathways to Change participants with non-participants, participants outperformed their non-participant counterparts in six categories but performed worse in five other categories that were not specifically targeted by the high-risk program. In two categories, no differences were found. The study underscores the ability of large-scale, well-attended, and comprehensive corporate health and productivity management programs to positively impact the health and well-being of workers.