Financial incentives are being used increasingly to encourage a wide array of health behaviors because of their well-established efficacy. However, little is known about how to translate incentive-based strategies to public health practice geared toward improving population-level health, and a dearth of research exists on how individuals respond to incentives through public health communication strategies such as direct mail. This study reports results of a population-based randomized controlled trial testing a direct mail, incentive-based intervention for promoting mammography uptake. The study population was composed of a random sample of Minnesota women enrolled in Medicare fee-for-service and overdue for breast cancer screening. Participants (N = 18,939) were randomized into three groups: (1) Direct Mail only, (2) Direct Mail plus Incentive, and (3) Control. Both direct mail groups received two mailers with a message about the importance of mammography; however, Mail plus Incentive mailers also offered a $25 incentive for getting a mammogram. Logistic regression analyses measured intervention effects. Results showed the odds for receiving mammography were significantly higher for the Direct Mail plus Incentive group compared with both Direct Mail only and Control groups. The use of incentives also proved to be cost-effective. Additionally, the Direct Mail only group was more likely to receive mammography than the Control group. Findings offer experimental evidence on how the population-based strategy of direct mail coupled with a financial incentive can encourage healthy behavior, as well as how incentive-based programs can be translated into health promotion practice aimed at achieving population-level impact.