To determine the utility of emergency physician-performed point-of-care biliary ultrasound in the evaluation of emergency department (ED) patients with isolated acute non-traumatic epigastric pain. This was a multi-center prospective observational study of adult patients presenting to the ED with isolated acute non-traumatic epigastric pain. Patients with abdominal tenderness at any site other than the epigastric region, or with a history of gall stones, cholecystectomy, gastrointestinal bleeding, chronic abdominal pain, trauma, or altered mental status were excluded. Emergency physician investigators performed point-of-care biliary ultrasound after clinical assessment. Demographic information, history, physical examination findings, laboratory results, additional diagnostic tests, and disposition data were collected. A total of 51 patients (39 women, 12 men) were enrolled. The mean age of the patients was 36.4 years ± 13.6 (SD). All subjects had isolated epigastric tenderness. Gallstones were found in 20/51 (39%, 95% CI 26-52%) on point-of-care biliary ultrasound. Of the 20 patients who had gallstones, eight had sonographic signs of chloecystitis. The treating emergency physicians' initial evaluation did not plan to include an ultrasound in 17/20 patients with gallstones. 19/20 patients were initially given a GI cocktail by the treating emergency physicians. Point-of-care biliary ultrasound detected gall stones in more than one-third of ED patients with isolated acute non-traumatic epigastric pain. All patients presenting to the ED with non-traumatic epigastric pain should be evaluated for biliary disease with an ultrasound imaging study. Bedside ultrasound can avoid misdiagnosis and expedite management in these patients.