IMPORTANCE Leishmaniasis is recognized as an endemic human disease in Africa, the Middle East, Asia, and South America. Yet despite case reports of endemic human leishmaniasis in the United States, and well-documented occurrences of disease in various animal vectors and reservoirs, the endemicity of leishmaniasis in North America has not yet been established. Moreover, leishmaniasis is not a federally reportable disease in the United States. Clinical awareness of endemic disease therefore remains low, with North American physicians considering leishmaniasis a tropical disease. OBJECTIVE To assess the endemicity of human leishmaniasis in the United States. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional multicenter observational study reviewed cases of human leishmaniasis occurring in the United States from 2007 through 2017. Previously diagnosed, deidentified cases of leishmaniasis were reported by the institutions of the authors and acknowledged contributors, as well as the Texas Department of State Health Services. Cases of leishmaniasis were identified by searching by disease name (leishmaniasis) or International Classification of Diseases, 9th and 10th Revisions diagnosis codes in the respective laboratory information systems. EXPOSURES Via examination of deidentified demographics, cases of leishmaniasis were classified as one of the following: (1) documentation of no history of travel outside of the United States within 10 years; (2) positive history of travel outside of the United States within 10 years; or (3) unknown or no documentation of travel history. MAIN OUTCOMES AND MEASURES Cases of leishmaniasiswere considered endemic if identified in patients with documentation of no travel history outside of the United States within 10 years. RESULTS Of the 69 novel cases of human cutaneous leishmaniasis identified in this study, 41 (59%) were endemic; the median age at diagnosis was 61 years (range, 3-89 years), and 28 (68%) of the endemic cases occurred in female patients. Twenty-two (32%) cases had documentation of Leishmania speciation performed by polymerase chain reaction, and in 100% of these cases the infectious organism was identified as Leishmania mexicana. CONCLUSIONS AND RELEVANCE Human cutaneous leishmaniasis is endemic in the United States, and, at least regionally, is acquired endemically more frequently than it is via travel. Our data argue in favor of making leishmaniasis a federally reportable disease and may have substantial implications on North American public health initiatives, with climate models predicting the number of citizens exposed to leishmaniasis will double by 2080.