Summary Background The field of laryngology has grown exponentially since the advent of the transnasal flexible laryngoscopy. Flexible laryngoscopy when performed skillfully using the proper technique, facilitates a good view of the hidden areas of the larynx. Objective To compare the effectiveness of the topical agents in providing a more comfortable experience for the patient, allowing the practitioner to advance the endoscope with less friction, pain and discomfort for the patient using 10% lidocaine spray, 2% lidocaine gel, 4% lidocaine with xylometazoline (1:1) soaked pledgets, or aqueous gel. Materials and Methods A prospective randomized single-blinded clinical trial was conducted in a tertiary care teaching hospital in South India where 376 patients were recruited and allocated into four groups based on the topical preparation used. Following endoscopy, each subject filled a questionnaire grading their experience on a visual analogue scale. The clinician also then answered a questionnaire on aspects of the endoscopy performed. Results The pain score and the ease of performing the procedure among the different groups were comparable. Those in the 10% lidocaine arm experienced significant burning sensation (P = 0.0001). The other variables such as throat pain (P = 0.783), gag reflex (P = 0.318), unpleasant taste (P = 0.092), globus (P = 0.190), swallowing difficulty after the procedure (P = 0.273), difficulty in breathing (P = 0.744) and willingness to have a repeat procedure (P = 0.883) were also comparable. Conclusion Aqueous gel can be used topically during a flexible nasopharyngolaryngoscopy instead of an anesthetic agent alone or one combined with a nasal decongestant.