OBJECTIVE To evaluate whether the gastrointestinal tract could be a source of chronic blood loss in premenopausal women with iron deficiency anemia. BACKGROUND While premenopausal women with iron deficiency anemia are typically managed with simple iron replacement, the standard of care for postmenopausal women and men is to exclude a gastrointestinal source of bleeding. METHODS We identified 111 premenopausal women who underwent endoscopy for the sole indication of iron deficiency anemia. RESULTS The mean age was 42.5 years. Lesions potentially causative of iron deficiency anemia were detected in 22 patients (20%). Upper gastrointestinal lesions were present in 14 patients (13%) and included only erosive lesions. Lower gastrointestinal lesions were detected in 8 patients (7.2%) and included colon cancer (2.7%), inflammatory bowel disease (3.6%), and a colonic ulcer >1 cm (0.9%). Patients with upper gastrointestinal lesions were more likely to use aspirin or nonsteroidal antiinflammatory drugs (11/14, 79%) than patients with no lesions (26/89, 23%; P = 0.043). Occult blood was more common in patients with lower gastrointestinal lesions 8/8 (100%) and patients with upper gastrointestinal lesions (9/14, 64%) than in patients without lesions (28/89, 31%; P = 0.037 and 0.039). Gastrointestinal symptoms were significantly more common in patients with gastrointestinal lesions than in patients without lesions. CONCLUSIONS A gastrointestinal source of chronic blood loss was identified in a substantial proportion of premenopausal women with iron deficiency anemia. Patients with gastrointestinal symptoms, fecal occult blood, and/or weight loss should undergo endoscopy.