Background: Occult gastrointestinal blood loss is generally investigated with colonoscopy and esophagogastroduodenoscopy in patients with iron-deficiency anemia. The aim of this study was to prospectively measure the additional diagnostic yield of examining the jejunum at the time of upper endoscopy in patients with iron-deficiency anemia. Methods: Asymptomatic patients with newly diagnosed iron-deficiency anemia who had no identifiable source of blood loss at colonoscopy underwent standard esophagogastroduodenoscopy with the Olympus SIF100L enteroscope followed by overtube-assisted enteroscopy. Upper tract and jejunal sources of blood loss were noted. Biopsy samples from the small bowel were taken when a bleeding lesion was not identified. Results: Thirty-one consecutive patients (13 men, mean age 71) with no gastrointestinal symptomatology were studied. Eleven patients (35%) had a bleeding source that required only esophagogastroduodenoscopy for identification; 8 patients (26%) had a source only in the jejunum; 2 patients (6%) (one with sprue) had a source in upper tract as well as jejunum. The enteroscopy was rated as causing minimal or mild discomfort in 25 of 31 patients (81%). Using Medicare reimbursement figures, a strategy of performing esophagogastroduodenoscopy first would have cost $656 per patient, whereas the strategy of performing esophagogastroduodenoscopy with enteroscopy as the initial test in all patients costs $467 per patient. Conclusions : Performance of push enteroscopy along with esophagogastroduodenoscopy increases the diagnostic yield from 41% to 67% when evaluating the upper gastrointestinal tract of asymptomatic patients with iron-deficiency anemia and, because of a lower cost, should be the preferred initial diagnostic test. (Gastrointest Endosc 1998:47:144-48)