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Blastomycosis is a disease caused by endemic fungi that ranges from severe pulmonary or disseminated to mild or asymptomatic. Environmental factors associated with it are not well described throughout the endemic area. We used the intramural State Inpatient Database from the Agency for Healthcare Research and Quality and ArcMap GIS to identify geographic high-risk clusters of blastomycosis hospitalizations in 13 states in the US endemic regions (AR, IA, IL, IN, KY, LA, MI, MN, MO, MS, OH, TN, and WI). We then used logistic regression to identify risk factors associated with these high-risk clusters. We describe six clusters of counties in which there was an elevated incidence of blastomycosis hospitalizations. We identified maximum mean annual temperature, percentage of persons aged ≥65 years, and mercury and copper soil content as being associated with high-risk clusters. Specifically, the odds of a county being part of a high-risk cluster was associated with increasing percentage of population over age 65, decreasing maximum temperature, increasing mercury, and decreasing copper soil content. Healthcare providers should be aware of these high-risk areas so that blastomycosis can be included, as appropriate, in a differential diagnosis for patients currently or previously residing in these areas.