Differences in patient tolerance, acceptance, and satisfaction of esophagogastroduodenoscopy (EGD) between transnasal (TN) and peroral (PO) routes using a 5-mm video endoscope. A total of 220 enrolled patients were assigned randomly to two groups undergoing EGD-110 patients each for TN and PO. The successful rate, procedure time, and adverse events were recorded. After the procedure, patients answered a validated questionnaire of tolerance, acceptance, and satisfaction. There were 6 failures (5.7%) of nasal intubation and two nasal bleeding (2%) among 105 TN-EGD procedures. All PO patients (n=102) completed EGD successfully without adverse event. Compared to PO, the procedure of TN achieved lower successful rate (94% vs. 100%, p=0.01), was complicated with epistaxis (2% vs. 0%) and took longer (mean ± SD 19.9 ± 6.1 min vs. 16.8 ± 6.4 min, p=0.0001). The patients undergoing TN-EGD indicated less discomfort during passing pharynx (scores of 2.1 ± 2.0 vs. 3.1 ± 2.6, p=0.011) but more pain during inserting scope (scores of 2.2 ± 1.6 vs. 1.5 ± 1.8, p=0.0001). Eventually, there were no significant differences between TN and PO regarding the overall procedure discomfort (scores of 10.7 ± 6.6 vs. 11.1 ± 7.8 scores, p=0.9), satisfaction (scores of 41.2 ± 4.2 vs. 41.3 ± 4.6, p=0.91), and acceptability (87.8% vs. 94.2%, p=0.91). PO intubation seems an excellent alternative method when using a 5-mm ultrathin endoscopy because it achieves comparable patient tolerance, acceptance, and satisfaction as TN intubation, takes less time and causes lower intubation failure and epistaxis.