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Objective A smartphone-enabled otoscope (SEO) can capture tympanic membrane (TM) images. We sought to compare a SEO to microscopic otoscopy in the detection and evaluation of TM pathology in an otology/neurotology practice. Study Design Prospective single-site study in adults presenting over a 3-month period. Setting Neurotology clinic within a tertiary care academic medical center. Subjects and Methods Following consent, 57 patients underwent a medical and microscopic ear examination. Afterward, clinicians photographed bilateral TMs using a SEO. A second "blinded" neurotologist received a SEO-acquired image of each TM and a brief patient history. Our primary end point was identification of TM pathology (or lack thereof) and the blinded neurotologists' corresponding diagnosis. Secondary end points included patient-reported SEO comfort levels. Results A single SEO-acquired TM image and brief patient history resulted in correct diagnosis of 96% (23/24) of normal TMs and identification of 100% (33/33) of microscope-confirmed abnormal TMs. When pathology was identified by the "blinded" physician, the diagnosis was identical to that made by the primary treating physician 82% (27/33) of the time. On patient surveys, 93% (53/57) of patients felt "very comfortable" with SEO utilization, and 88% (50/57) reported viewing acquired images was "very useful" in understanding their condition. Conclusion A SEO is 96% specific in identifying normal TMs and 100% sensitive in identifying pathology. Its 97% positive predictive value and small false-positive rate makes it a useful screening tool. Furthermore, patients are receptive to this technology and felt comfortable with its utilization in a health care or possible telemedicine setting.