Studies show that aspirin is very effective as secondary prevention of cardiovascular events, however its use for primary prevention of cardiovascular disease (CVD) is questionable. There are clinical trials performed to study its effectiveness for primary prevention, however cost-effectiveness studies have not been done to see the tradeoff between decreased CVD and increased adverse events. OBJECTIVES: Primarily, this paper seeks to calculate the incremental cost-effectiveness ratios (ICERs) of using aspirin in males and females aged 40-80 with no prior history of CVD. Secondarily, to calculate the ICERs of HMG-CoA Reductase Inhibitors compared to aspirin. METHODS: The cost-effectiveness ratios were calculated for a hypothetical cohort of patients using a decision analytic spreadsheet model with a societal perspective in 2001 U.S. Dollars. Measurements of costs, effectiveness, utilities, and rates of events were obtained from literature. A series of 1-way sensitivity analyses were performed to test the robustness of the model. For the secondary objective, the incremental costs and incremental CVD risk reduction obtained from using HMG-CoA Reductase Inhibitors instead of aspirin is applied to the model to obtain ICERs of HMG-CoA Reductase Inhibitors compared to aspirin. RESULTS: The base-case results of the model show that the highest ICER in males is $2,932/QALY, and for females is $5,441/QALY. One-way sensitivity analyses show the variable with the highest variance in cost/QALY results in an ICER of $12,252/QALY. Secondary analysis shows the ICERs for males and females using HMG-CoA Reductase Inhibitors compared to aspirin are under $26,000/QALY for all ages. CONCLUSION: This research study shows that the use of prophylaxis aspirin (75mg/day) is cost-effective for the primary prevention of CVD in males and females aged 40-80. The use of HMG-CoA Reductase Inhibitors compared to aspirin provides higher effectiveness but at higher costs, resulting in ICERs up to $26,000/QALY.