Background: The trigemino-cardiac reflex (TCR) is a sudden onset of bradycardia, hypotension, apnea or gastric hypermotility during stimulation of the trigeminal nerve. Methods: We conducted a MEDLINE search for surgical cases of TCR and herein describe a case seen recently at our institution. Results: A 60 year-old female underwent a left orbitozygomatic craniotomy for resection of a skull-base tumor. Pre-operative anesthesia evaluation was unremarkable and negative for a history of cardiovascular disease. Intra-operatively, retraction with moderate force of the temporalis muscle consistently produced asystole. Cessation of retraction resulted in immediate return of sinus rhythm. Otherwise, intra-operative heart rate was 60-90 BPM. Post-operatively, vital signs and clinical course were unremarkable. The patient experienced a similar phenomenon during an operation 6 years earlier, when manipulation of tumor near cranial nerves IX/X resulted in bradycardia. TCR is the result of a polysynaptic brainstem network involving the afferent trigeminal sensory nucleus, the reticular formation, and the efferent vagal motor nucleus. Conclusions: This is a case of exaggerated vagal response following manipulation of the temporalis muscle. Our report emphasizes the importance for neurosurgeons and anesthesiologists alike to be wary of TCR in order to avoid deleterious consequences when operating on structures associated with the trigeminal nerve.