Objectives/Hypothesis: Use of topical nasal anesthetic (TNA) is common in high-resolution impedance manometry (HRIM). This study investigated the effect of TNA on swallowing and procedure tolerability during HRIM with a 4.2-mm catheter, a more commonly used catheter size with impedance capabilities.Study Design: Randomised experimental study with blinding of participants. Methods: Twenty healthy participants (mean age = 33 years, 16 female) were randomized to undergo HRIM using the ManoScan™ ESO Z 4.2-mm catheter twice, 1 week apart, under two conditions: with TNA (viscous lidocaine) and with placebo. Analyses included esophageal data of three saliva, three saline (5 mL), and three bread swallows (2 cm  2 cm) performed while reclined 45 , and pharyngeal data under the same conditions while seated upright. Pharyngeal and upper esophageal sphincter (UES) HRIM parameters were analyzed using the Swallow Gateway analysis platform. Visual analogue scale (VAS) scores rating procedural comfort were analyzed.Results: There were no significant physiological differences in pharyngeal and UES parameters between conditions. There were also no significant differences in VAS scores under placebo (mean = 54.8, standard deviation (SD) = 19.3) and TNA (mean = 60.0, SD = 21.9) (t[19] = À0.9, P = .4) conditions; however, there was a significant difference in the first versus second session (t[19]) = 5.1, P < .05).Conclusions: TNA did not improve comfort, but it also did not significantly affect swallowing behavior. There was, however, a practice effect regardless of TNA use with improved tolerance of the 4.2-mm catheter and likely more natural swallowing behavior during the second session of HRIM.