OBJECTIVE: A Markov model was developed to compare the cost-utility of statins available via prescription (Rx) versus hypothetical over the counter (OTC) status in the USA. METHODS: Cost-utility of Rx statins and hypothetical OTC statins was ascertained from a societal perspective in US dollars expended per quality-adjusted life-years ($/QALYs) using a Markov model over 10 years. The probability rates for coronary events and coronary deaths were obtained from 8 randomized clinical trials, and rate of adverse drug events were obtained from national prescribing services. Baseline costs (including drugs, adverse events, cardiovascular events, physician visits) and health outcomes were discounted at 5% annually. Average acquisition and dispensing costs for Rx statins were compared to the assumed average lower dose costs for potential OTC statins in the United States. RESULTS: Based on societal drug acquisition costs with basic assumptions, OTC statins would be less expensive as compared to the Rx statins. OTC statins had a calculated cost-utility of $1434/ QALY compared to $1867/ QALY for Rx statins. Varying the discount rate simultaneously for cost and QALYs from 0%-10% resulted in a $/QALY gained for Rx ranging from $1899 to $1836 respectively, compared to the OTC range of $1472 to $1398. CONCLUSION: Rx statins with baseline assumptions had a higher percent LDL reduction and fewer coronary events. Rx statins had higher cost per QALYs gained and OTC statins were observed to be the optimal strategy choice. More research is needed on the impact of statins over the counter, including appropriate assessment of lab monitoring, adverse event monitoring and compliance and adherence measures to facilitate a better understanding of the clinical and economic outcomes. Availability of future lipid lowering drugs with varying acquisition costs and potency will require further analyses.