Allergies are among the most common chronic conditions. About two thirds of the population have experienced allergic symptoms in their lives. In the U.S., the prevalence rate is estimated to be as high as 15%, representing 40 to 50 million individuals. Over half of the U.S. population has tested positive for one or more allergens.   OBJECTIVES: The objective of this study was to determine the utilization and expenditure trends for anti-allergic agents in the U.S. Medicaid program.    METHODS: A retrospective, descriptive analysis was conducted. We extracted the utilization and expenditure data from the national Medicaid pharmacy files, which  cover 1991 first quarter to 2011 second quarter. The study drugs included first-generation antihistamines (e.g. brompheneramine, chlorpheniramine, doxylamine, and pheniramine) and second-generation antihistamines (e.g. azelastine, cetirizine, desloratadine, levocertizine, and loratadine). The quarterly prescription numbers and reimbursement amounts were calculated over time by summing data for individual drug products. The quarterly per-prescription reimbursement as a proxy for drug price was computed for each study drug. RESULTS: The total number of prescriptions for anti-allergic drugs reached a peak of 18.7 million in 2003. The prescriptions for first-generation antihistamines dominated the market from 1991 to 1998, while the prescription market share for second-generation antihistamines increased from 12.84% in 1991 first quarter to 57.17% in 2011 second quarter. From 1991 to 2002, the total annual Medicaid expenditures for antihistamines grew from $87.7 million to $757.2 million, a rapid increase. The average annual per-prescription price of first-generation antihistamines fluctuated between $8 and $17, while the per-prescription price of second-generation antihistamines increased from $13 to $64 from 1991 to 2011. CONCLUSIONS: Although the U.S. Medicaid Program encourages switching to over-the-counter medications when available, which may be outside of the study’s database, utilization of and expenditures on anti-allergic medications have nevertheless risen substantially over the last two decades.