Dysphagia is not uncommon after curative treatment for primary head and neck cancer. Local recurrences or second primary cancers in the upper digestive tract need to be excluded firstly before treatment for dysphagia. However, many patients have trismus or pharyngeal stenosis following treatment, both of which prevent rigid/flexible transoral laryngoscopy/esophagoscopy evaluating the entire upper digestive tract. The purpose of this study was to prospectively investigate the diagnostic value of unsedated transnasal esophagogastroduodenoscopy (EGD) in 36 primary head and neck cancer patients with post-treatment dysphagia. Except three patients with very narrow space or the presence of the tumor in the neopharynx, transnasal EGD could completely evaluate the upper digestive tract in 33 patients and found one patient with local recurrent hypopharyngeal cancer, seven patients with newly diagnosed hypopharyngeal cancer, four patients with esophageal cancer, and one patient with simultaneous hypopharyngeal and esophageal cancers, which were all successfully biopsied and proven microscopically. Five patients previously receiving total laryngectomy had various degrees of stenosis of the neopharynx without local recurrence or esophageal cancer. Thirteen patients had no significant organic or pathological lesions. One patient had a benign tumor on the epiglottis and the other NPC patient had extensive soft tissue necrosis in the pyriform sinus as a cause of dysphagia. The mean duration of the entire procedure was 16min. All patients tolerated the procedure well. No significant complications were noted during and after examination. The present study indicates that unsedated transnasal EGD is feasible to confidently distinguish between functionally/anatomically-related dysphagia and newly growing tumors in the upper digestive tract, and to obtain biopsy specimens for pathological diagnosis from the tumors in a single session.