There is, currently, no consensus with regard to the role of endoscopy in the etiologic investigation of asymptomatic pemenopausal women suffering from iron deficiency anemia (IDA). We conducted a retrospective case-control study to evaluate the contribution of esophagogastroduodenoscopy (EGD) and colonoscopy to the etiologic diagnosis of a group of asymptomatic premenopausal women suffering from IDA. One hundred eight consecutive asymptomatic premenopausal women who fulfilled our entry criteria were included in our patient group between January 1998 and December 2004. One hundred thirty-five age-matched asymptomatic premenopausal women without anemia who had undergone EGD and colonoscopy for medical checkups were included in the control group. Clinically relevant lesions were detected in 7 of 108 (6.5%) of the patients and in 8 of 135 (5.9%) of the controls. There were no differences with regard to the frequency of clinically relevant lesions between the two groups (P > 0.05). Concomitant upper and lower GI lesions were not detected in any patients. In the upper GI tract, the only lesion found to be potentially causative of IDA anemia was a severe erosive gastritis, which was found in both the patient and the control groups. A source consistent with chronic bleeding was detected in the lower GI tract in 6 (5.6%) of the patients and 7 (5.2%) of the controls. Bleeding hemorrhoids represented the most frequently detected lesions in both the patient and control groups. Only one case of colon cancer was detected in the patient group. As IDA in the premenopausal women could not be attributed consistently to GI blood loss in this study, prospective studies should be conducted to validate our findings and to identify which subgroup of asymptomatic premenopausal women would benefit from a diagnostic endoscopic evaluation.