No / The aim of this prospective randomized study was to evaluate the role of carbon dioxide (CO2) and normal saline for diagnostic accuracy in out-patient hysteroscopy. Women admitted to our Department in order to undergo total abdominal hysterectomy also underwent diagnostic hysteroscopy, 12¿24 h prior to surgery. The selection of distending medium was made after randomization. Two groups of patients were formed, group A (CO2; n=39) and group B (normal saline; n=35). More than half of the women in the study population were post-menopausal. Post-hysteroscopy, all women were asked to rank any symptom that they felt during the procedure on a 4-point scale (0 = none; 1 = mild; 2 = severe; 3 = inability to perform hysteroscopy). The hysteroscopic diagnosis was compared with the macroscopic findings and the histological examination of the surgical specimen after hysterectomy. The percentage who completed hysteroscopy was 89.74% within group A and 97.14% within group B. Most patients of both groups felt some pain of mild intensity. The diagnostic accuracy of hysteroscopy was similar for both media when major pathology [large polyps (group A 91.7%; group B 92.7%), myomas (group A 81.25%; group B 92.7%) and/or hyperplasia (group A 87.5%; group B 90.2%)] of the endometrial cavity was detected. In contrast, in cases of minor pathology (small polyps, mucosal elevations, crypts, hypervascularization), hysteroscopy with saline presented with significantly higher diagnostic accuracy (85.4%) compared with hysteroscopy with CO2 (64.6%). In out-patient hysteroscopy, CO2 and normal saline were comparable with regard to patient discomfort and for the detection of major pathology of the endometrial cavity. Normal saline seems to be the most appropriate medium for the detection of minor pathology of the endometrial cavity.