In this multicenter, prospective, cross-sectional study, 422 patients (mean age 55.8 ± 9 years) from a general medical clinic population underwent unsedated office-based transnasal esophagoscopy. The procedure was feasible, safe and well-tolerated, and the management of 38% of patients was changed in response to esophageal findings of erosive esophagitis or Barrett esophagus.