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Propofol sedation has been applied during esophagogastroduodenoscopy procedures, but whether topical pharyngeal anesthesia should be administered at the same time has rarely been reported. Our study examined the role of topical pharyngeal anesthesia in sedated endoscopies in a randomized controlled double-blinded clinical trial. A total of 626 patients who underwent sedated esophagogastroduodenoscopy were randomized into the experimental group (n = 313) or the control group (n = 313). The discomfort score, immediately and one day after the procedure, was not statistically significant [7.2 (5–9) vs. 7.5 (6–9), P = 0.210; 2.3 (0–3) vs. 2.6 (0–4), P = 0.095, respectively]. Two patients in the experimental group and three patients in the control group needed oral medication for pharyngeal discomfort (P = 0.354). The satisfaction score was 9.2 (8–10) in the experimental group and 8.9 (7–10) in the control group (P = 0.778). Lidocaine topical pharyngeal anesthesia in propofol-sedated esophagogastroduodenoscopy did not further reduce the pharyngeal discomfort or improve the satisfaction. This clinical trial was registered at ClinicalTrials.gov (ClinicalTrials.gov ID: NCT03070379).