Objective: The aim of this study was to determine the annual direct costs of treating bacterial conjunctivitis (BC) in the United States. Methods: A systematic review of the medical literature was supplemented with information from detailed physician interviews on resource utilization associated with bacterial conjunctivitis therapy in the United States. Data on the annual incidence of BC was obtained from an analysis of the National Ambulatory Medical Care Survey (NAMCS) database for the year 2005. Cost estimates for resource utilization such as physician visits and prescription drugs were taken from standard cost reference sources. Due to the acute nature of BC no cost discounting was performed. The economic perspective presented is that of the payer. All costs are expressed in 2007 U.S. dollars. Results: The number of BC cases in the United States for 2005 was estimated at 4,016,544, yielding an estimated annual incidence rate of 135.46 per 10,000. Base-case analysis estimated the direct cost of treating patients with bacterial conjunctivitis in the United States at US$765,063,696. One-way sensitivity analysis assuming either a 20% variation in the annual incidence of bacterial conjunctivitis or treatment costs generated a cost range of US$612,050,957 to US$918,076,435. Two-way sensitivity analysis assuming a 20% variation in both the annual incidence of bacterial conjunctivitis and treatment costs occurring simultaneously resulted in an estimate cost range of US$489,627,912 to US$1,101,711,002. Conclusion: This study reports the first known estimate of the direct costs of treating and managing patients with bacterial conjunctivitis in the United States. The economic burden of this condition is substantial. Our estimates represent conservative amounts because indirect costs were not considered in the analysis. This information may prove useful to decision makers with respect to the adequate allocation of health care resources necessary to address the economic burden of BC in the United States.