Objective Assess the influence of participation in a population health management (PHM) program on health care costs. Methods A quasi-experimental study relied on logistic and ordinary least squares regression models to compare the costs of program participants with those of nonparticipants, while controlling for differences in health care costs and utilization, demographics, and health status. Propensity score models were developed and analyses were weighted by inverse propensity scores to control for selection bias. Results Study models yielded an estimated savings of $60.65 per wellness participant per month and $214.66 per disease management participant per month. Program savings were combined to yield an integrated return-on-investment of $3 in savings for every dollar invested. Conclusions A PHM program yielded a positive return on investment after 2 years of wellness program and 1 year of integrated disease management program launch.