Background & Aims: Significant portions of-the cost and complications of esophagogastroduodenoscopy (EGD) are related to sedation, This study aimed to assess the feasibility, acceptability, and accuracy of unsedated small-caliber transoral EGD (sc-EGD), Methods: A 4-phase study was performed in healthy volunteers and patients. Phases 1 and 2 involved assessment of the technical feasibility of sedated sc-EGD and the tolerability of unsedated sc-EGD, respectively, in volunteers. Subsequently, the technical feasibility, tolerability, and diagnostic accuracy of sedated and unsedated sc-EGD were determined by having each patient undergo sc-EGD (Pentax EG-1840) with (phase 3) and without (phase 4) sedation, followed by sedated conventional EGD (c-EGD) (Olympus GIF-100 or GIF-Q140) by a staff endoscopist blinded to the findings of the sc-EGD, The t test for paired samples was used for statistical analysis, A P value of < 0.05 was considered significant. Results: Sedated and unsedated sc-EGD were technically feasible and tolerable in all volunteers. In patients, compared with sedated c-EGD, sedated and unsedated sc-EGD were 96% and 97% accurate, respectively. The overall acceptability of unsedated sc-EGD was only slightly worse than that of sedated c-EGD (median, 2 vs. 1 on a scale of 1-10), After unsedated sc-EGD, 98% of patients expressed willingness to undergo the procedure again, No complications were observed during any phase of the study. Conclusions: Unsedated sc-EGD is technically feasible, tolerable, and accurate, It can potentially decrease the costs and complications of sedated conventional EGD.