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BACKGROUND: The Diabetes Prevention Program (DPP) demonstrated that interventions can delay or prevent the development of type 2 diabetes. OBJECTIVE: To estimate the lifetime cost-utility of the DPP interventions. DESIGN: Markov simulation model to estimate progression of disease, costs, and quality of life. DATA SOURCES: The DPP and published reports. TARGET POPULATION: Members of the DPP cohort 25 years of age or older with impaired glucose tolerance. TIME HORIZON: Lifetime. PERSPECTIVES: Health system and societal. INTERVENTIONS: Intensive lifestyle, metformin, and placebo interventions as implemented in the DPP. OUTCOME MEASURES: Cumulative incidence of diabetes, microvascular and neuropathic complications, cardiovascular complications, survival, direct medical and direct nonmedical costs, quality-adjusted life-years (QALYs), and cost per QALY. RESULTS OF BASE-CASE ANALYSIS: Compared with the placebo intervention, the lifestyle and metformin interventions were estimated to delay the development of type 2 diabetes by 11 and 3 years, respectively, and to reduce the absolute incidence of diabetes by 20% and 8%, respectively. The cumulative incidence of microvascular, neuropathic, and cardiovascular complications were reduced and survival was improved by 0.5 and 0.2 years. Compared with the placebo intervention, the cost per QALY was approximately 1100 dollars for the lifestyle intervention and $31 300 for the metformin intervention. From a societal perspective, the interventions cost approximately 8800 dollars and 29,900 dollars per QALY, respectively. From both perspectives, the lifestyle intervention dominated the metformin intervention. RESULTS OF SENSITIVITY ANALYSIS: Cost-effectiveness improved when the interventions were implemented as they might be in routine clinical practice. The lifestyle intervention was cost-effective in all age groups. The metformin intervention did not represent good use of resources for persons older than 65 years of age. LIMITATIONS: Simulation results depend on the accuracy of the underlying assumptions, including participant adherence. CONCLUSIONS: Health policy should promote diabetes prevention in high-risk individuals.