Background: Aspirin and statins are both effective for primary prevention of coronary heart disease (CHD), but their combined use has not been well studied. Objective: To perform a cost-utility analysis of the effects of aspirin therapy, statin therapy, combination therapy with both drugs, and no pharmacotherapy for the primary prevention of CHD events in men. Design: Markov model. Data Sources: Published literature. Target Population: Middle-aged men without a history of cardiovascular disease at 6 levels of 10-year risk for CHD (2.5%, 5%, 7.5%, 10%, 15%, and 25%). Time Horizon: Lifetime. Perspective: Third-party payer. Interventions: Low-dose aspirin, a statin, both drugs as combination therapy, or no therapy. Outcome Measure: Cost per quality-adjusted life-year gained. Results of Base-Case Analysis: For 45-year-old men who do not smoke, are not hypertensive, and have a 10-year risk for CHD of 7.5%, aspirin was more effective and less costly than no treatment. The addition of a statin to aspirin therapy produced an incremental cost-utility ratio of $56 200 per quality-adjusted life-year gained compared with aspirin alone. Results of Sensitivity Analysis: Excess risk for hemorrhagic stroke and gastrointestinal bleeding with aspirin, risk for CHD, the cost of statins, and the disutility of taking medication had important effects on the cost-utility ratios. Limitations: Several input parameters, particularly adverse event rates and utility values, are supported by limited empirical data. Results are applicable to middle-aged men only. Conclusions: Compared with no treatment, aspirin is less costly and more effective for preventing CHID events in middle-aged men whose 10-year risk for CHID is 7.5% or higher. The addition of a statin to aspirin therapy becomes more cost-effective when the patient's 10-year CHD risk before treatment is higher than 10%.