Background: The aim of this study was to assess the yield of antral biopsies performed via unsedated transnasal esophagogastroduodenoscopy, a technique that does not require conscious sedation with its concomitant costs and complications, for documentation of Helicobacter pylori eradication. Methods: Nineteen patients who were previously CLO test positive on conventional esophagogastroduodenoscopy and subsequently treated for H pylori infection were enrolled. The subjects had not received antibiotic therapy in the prior month and had no prior gastric surgery. By using a GIF-N30 fiberoptic endoscope and a tiny cup biopsy forceps (1.8 mm diameter), unsedated transnasal endoscopy was performed and antral biopsy specimens were taken for a CLO test, histologic analysis (Dieterle stain), and tissue culture. On the same day, the subjects underwent a carbon 13-labeled area urea breath test. All subjects completed a visual analog scale, rating the acceptability of the unsedated transnasal examination and the previous sedated conventional esophagogastroduodenoscopy. Results: There was no statistically significant difference between the results of the CLO tests (5/19 positive) versus the 13C-urea breath test (4/19 positive) (p = 0.96), the CLO tests versus histologic findings (5/19 positive) (p = 0.71), or the 13C-urea breath test versus histologic findings (p = 0.96). All tissue culture results were negative. The overall acceptability of unsedated transnasal esophagogastroduodenoscopy was similar to that of sedated conventional esophagogastroduodenoscopy. Conclusion: Unsedated transnasal esophagogastroduodenoscopy, a technique that eliminates the costs and complications associated with conscious sedation, is a feasible and accurate alternative to conventional esophagogastroduodenoscopy when documentation of H pylori eradication and confirmation of gastric ulcer healing are both indicated.