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Background: The Trigemino-cardiac reflex (TCR) has been studied as a phenomenon including; bradycardia, arterial hypotension, apnea and gastric hypermotility during manipulation of the peripheral or central parts of the trigeminal nerve. Case presentation: We report a case of a 26-year-old man undergoing surgery for a skull base extra axial tumor in right petrous bone suspected to metastasis of a previous renal cell carcinoma which had been treated four years ago. The patient presented with continuous and unilateral headache and difficulty in swallowing, sensory neural hearing loss, nasal speech and tongue deviation to left side. He underwent general anesthesia with standard monitoring and total intravenous anesthetic technique. The first episode of sudden onset bradycardia and hypotension related to surgical manipulation was detected intraoperatively in which the heart rate spontaneously returned to normal level once the surgical manipulation stopped. However, it repeated several times by beginning of tumor resection and manipulation in the region of trigeminal nerve. The intensity of bradycardia in subsequent episodes of TCR was relatively crescendo and had no fatigability. Finally, it was treated by administration of a single dose of atropine (0.5mg/IV) and did not happen again. Conclusion: The risk of TCR should be considered in any neurosurgical intervention involving trigeminal nerve and its branches, especially at the skull base surgeries. The vigilance of the medical team and continuous intraoperative hemodynamic monitoring alerts the surgeons to interrupt surgical maneuvers upon the TCR occurrence, immediately. [ABSTRACT FROM AUTHOR]