BACKGROUND: Endoscopic screening for esophageal neoplasia can identify patients eligible for early intervention for precancerous lesions. Unsedated transnasal esophagoscopy may provide an efficient and accurate endoscopic assessment with fewer risks and less cost, compared with conventional upper endoscopy. OBJECTIVE: To assess the feasibility, safety, acceptability, and yield of unsedated transnasal esophagoscopy in a primary care population. DESIGN: Multicenter, prospective, cross-sectional study. SETTING: Two outpatient tertiary-care centers. PATIENTS: This study involved a general medical clinic population aged between 40 and 85 years. INTERVENTION: Unsedated, office-based transnasal esophagoscopy. MAIN OUTCOME MEASUREMENTS: Procedure yield; completeness of examination; procedure length; adverse events and complications; choking, gagging, pain, or anxiety during the examination; and overall tolerability. RESULTS: A total of 426 participants (mean [± standard deviation] age 55.8 ± 9.5 years; 43% male) enrolled in the study, and 422 (99%) completed the examination. Mean (± standard deviation) examination time was 3.7 ± 1.8 minutes. There were no serious adverse events, and 12 participants (2.8%) reported minor complications. Participants reported minimal choking, gagging, pain, or anxiety. The examination was well-tolerated by most participants. Overall, 38% of participants had an esophageal finding that changed management (34% erosive esophagitis, 4% Barrett's esophagus). LIMITATIONS: Nonrandomized study, tertiary-care centers only, self-selected population with a large proportion reporting esophageal symptoms. CONCLUSION: Unsedated transnasal esophagoscopy is a feasible, safe, and well-tolerated method to screen for esophageal disease in a primary care population. Endoscopic findings are common in this patient population.