Transnasal oesophagogastroduodenoscopy (OGD) with a narrow-bore endoscope has been demonstrated to be feasible in unsedated volunteers. The aim of the study was to compare efficacy, safety, patient tolerance and costs between this novel approach to OGD and standard sedated OGD. Sixty day patients were enrolled for either sedated transoral endoscopy with a standard calibre endoscope or for unsedated transnasal endoscopy with a narrow-bore (5.3 mm diameter) endoscope. Visualization was unsatisfactory in one examination in each group. The only complications were minor epistaxis in four of the transnasal group and oxygen desaturation below 90% in two of the sedated transoral group. On a 1 (very uncomfortable) to 5 (very comfortable) visual analogue scale, the mean transnasal group score was 3.09, compared with 3.86 in the transoral group (P = 0.013). In the transnasal group, mean procedure room time was 15 min compared with 20 min in the transoral group (P < 0.0003), and mean recovery room time was 7 min compared with 37 min (P < 0.0001). Consumable and pharmaceutical costs were reduced by 65 and 92%, respectively. This study demonstrates that unsedated transnasal OGD is a safe and effective route for OGD and has acceptable patient tolerance. The safety and decreased recovery times offer major cost savings and the potential for this method of OGD to become an office procedure for the investigation of the upper gastrointestinal tract.