The trigeminocardiac reflex (TCR) is clinically defined as the sudden onset of increased parasympathetic activity resulting from stimulation of the trigeminal nerve. This reflex increases parasympathetic tone and can lead to significant bradycardia and hypotension. We report the case of severe bradycardia and hypotension that occurred under general anesthesia during insertion of a cotton swab into the nasal cavity. A 57-year-old woman was scheduled for nasotracheal intubation for oral surgery, and following loss of consciousness, intubation was initiated using cotton swabs soaked in a solution of 2% lidocaine and 1:100,000 epinephrine that were inserted through the left nostril. The patient immediately developed severe bradycardia and hypotension which were managed with intravenous ephedrine after removing the cotton swabs rather than atropine due to concerns related to closed-angle glaucoma. The patient responded promptly to the ephedrine bolus, and no further complications occurred. It was assumed that the ophthalmic (V1) and maxillary (V2) branches of the trigeminal nerve were stimulated by the cotton swabs being inserted into the nasal cavity, triggering the TCR. Anesthesiologists need to be aware of the risks associated with administering mydriatic drugs such as ephedrine and epinephrine, which are relatively contraindicated, as well as atropine to patients with closed-angle glaucoma.