The impact of pollen exposure on population allergic illness is poorly characterized. We explore the association of tree pollen and over-the-counter daily allergy medication sales in the New York City metropolitan area. Dates of peak tree pollen (maple, oak, and birch) concentrations were identified from 2003 to 2008. Daily allergy medication sales reported to the city health department were analyzed as a function of the same-day and lagged tree pollen peak indicators, adjusting for season, year, temperature, and day of week. Significant associations were found between tree pollen peaks and allergy medication sales, with the strongest association at 2-day lag (excess sales of 28.7% (95% CI: 17.4–41.2) over the average sales during the study period). The cumulative effect over the 7-day period on and after the tree pollen peak dates was estimated to be 141.1% (95% CI: 79.4–224.1). In conclusion, tree pollen concentration peaks were followed by large increases in over-the-counter allergy medication sales.