OBJECTIVE: To evaluate the factors influencing the utilization of prescribed medications across the United States. METHODS: Prescription claims data for a random sample of commercially insured Express Scripts members, 18–64 years of age and continuously eligible for at least two months in 1999 (N=1,467,699), were geo-coded at the block group level. Key independent variables included age, gender, family size, median income, education, urban/rural location, client type, and pharmacy benefit design. Outcome measures included any use of prescriptions. Hierarchical modeling (HLM) was used to control for clustering of patients within health plans. RESULTS: Results from HLM indicate that after controlling for demographics, client type, and pharmacy benefit design, variation in the probability of using a prescribed medication was found across regions of the country. Members in the South have a greater likelihood of use and members in the Northeast and West having a lower probability of use than members in the Midwest. A greater probability of use was associated with older age, female gender, higher income, family size >1, and enrollment in a managed care plan. Factors associated with lower probability of prescription use included presence of a deductible, living in an urban area and having a mandatory generic policy. CONCLUSIONS: While patient age and gender remain key factors driving prescription utilization, socioeconomics, pharmacy benefit design, and where a person lives are also predictors of prescription use. Future research is needed to better understand the causative roles of disease burden, physician practice style, and consumer preferences in prescription drug use variation across the United States. Cancer I