Topical steroids are the primary medical therapy for eosinophilic esophagitis (EoE). Current steroid formulations are used off-label and designed for airway delivery. It is known that the efficacy of topical steroids depends on drug-mucosal contact time, which is related to its formulation. The purpose of this study is to examine the effectiveness of fluticasone administered by means of an orally administered powder formulation. We conducted a retrospective analysis of patients diagnosed with EoE based on current guidelines and who were treated with orally administered fluticasone powder. The primary outcome was histologic response (peak eosinophil density (eos/hpf)). Secondary outcomes included patient-reported symptoms (EoEQ) and endoscopic features measured by a validated instrument (EoE endoscopic reference score, EREFS). Forty patients were treated with fluticasone powder with doses of 500 to 1000 mcg b.i.d. A significant difference was found between pre- and posttreatment levels of eosinophilia (P < 0.0001). Seventy-five percent of patients achieved peak densities of <15 eos/hpf. Improvement was also demonstrated in dysphagia symptoms (P = 0.031) and endoscopic findings of furrows (P = 0.0001) and exudates (P = 0.0001). Oral fluticasone powder induced significant improvement in histopathology, symptoms, and endoscopic features of inflammation in adults with EoE. It offers an easy-to-administer formulation of a topical steroid that circumvents concerns with esophageal delivery of commonly used, aerosolized inhaler preparations.