Purpose: To estimate the relationship between employees’ health risks and health-care costs to inform health promotion program design. Design: An observational study of person-level health-care claims and health risk assessment (HRA) data that used regression models to estimate the relationship between 10 modifiable risk factors and subsequent year 1 health-care costs. Setting: United States. Participants: The sample included active, full-time, adult employees continuously enrolled in employer-sponsored health insurance plans contributing to IBM MarketScan Research Databases who completed an HRA. Study criteria were met by 135 219 employees from 11 employers. Measures: Ten modifiable risk factors and individual sociodemographic and health characteristics were included in the models as independent variables. Five settings of health-care costs were outcomes in addition to total expenditures. Analysis: After building the analytic file, we estimated generalized linear models and conducted postestimation bootstrapping. Results: Health-care costs were significantly higher for employees at higher risk for blood glucose, obesity, stress, depression, and physical inactivity (all at P <.0001) than for those at lower risk. Similar cost differentials were found when specific health-care services were examined. Conclusion: Employers may achieve cost savings in the short run by implementing comprehensive health promotion programs that focus on decreasing multiple health risks.