We conducted a randomized controlled trial to compare ultrathin (UT-EGD) and conventional esophagogastroduodenoscopy (C-EGD) in unsedated adults with or without local pharyngeal anaesthesia (LPA). Methods: Four hundred patients (248 female; mean age 43.1) undergoing EGD were randomized into four groups (UT-EGD with LPA, n = 100; UT-EGD with placebo, n = 100; C-EGD with LPA, n = 100; C-EGD with placebo, n = 100). All patients had no experience of previous EGD and were blinded from the intervention. Outcome measures included post-procedure throat pain in visual analog scale (VAS), patient tolerance in VAS, satisfaction score in VAS and patient's willingness to repeat procedure. Results: All patients had complete examination with successful duodenal intubation. There was no significant interaction effect between the type of endoscope and LPA in all outcome parameters (2-way ANOVA). UT-EGD significantly improved post-procedure throat pain (1.66 vs 2.54; p < 0.001) and patient tolerance (5.96 vs 5.18; p = 0.004) when compared to C-EGD. LPA significantly improved patient tolerance (6.08 vs 5.06; p < 0.001) when compared to placebo with no effect on post-procedure throat pain. No significant difference was found in satisfactory score and willingness to repeat procedure between groups. Conclusions: Routine implementation of UT-EGD and LPA are recommended to improve post-procedure throat pain and patient tolerance during unsedated EGD.