Although many employers offer some components of worksite-based population health management (PHM), most do not yet invest in comprehensive programs. This hesitation to invest in comprehensive programs may be attributed to numerous factors, such as other more pressing business priorities, reluctance to intervene in the personal health choices of employees, or insufficient funds for employee health. Many decision makers also remain skeptical about whether investment in comprehensive programs will produce a financial return on investment (ROI). Most peer-reviewed studies assessing the financial impact of PHM were published before 2000 and include a broad array of program and study designs. Many of these studies have also included indirect productivity savings in their assessment of financial outcomes. In contrast, this review includes only peer-reviewed studies of the direct health care cost impact of comprehensive PHM programs that meet rigorous methodological criteria. A systematic search of health sciences databases identified only 5 studies with program designs and study methods meeting these selection criteria published after 2007. This focused review found that comprehensive PHM programs can yield a positive ROI based on their impact on direct health care costs, but the level of ROI achieved was lower than that reported by literature reviews with less focused and restrictive qualifying criteria. To yield substantial short-term health care cost savings, the longer term financial return that can credibly be associated with a comprehensive, prevention-oriented population health program must be augmented by other financial impact strategies.