Objective To investigate the predictive factors of trigemino‑cardiac reflex (TCR) in pituitary tumor resection and the effect of TCR on cardiac adverse events in patients after surgery. Methods This was a single‑center retrospective case‑control study. Patients undergoing elective pituitary tumor resection from October 1, 2015 to September 30, 2020 in Beijing Tiantan Hospital, Capital Medical University were enrolled and their data were retrospective analyzed. Their demographic characteristics, baseline information (heart rate, mean arterial pressure, and electrocardiogram), surgical and anesthesia information, tumor characteristics (tumor size, invasion, and pathologic type), myocardial enzyme, and preoperative or intraoperative antiarrhythmic drug used were collected. Patients in the case group were screened according to the TCR criteria for sudden relative bradycardia (deceleration of heart rate more than 20% of baseline) when stimulating any branch of the trigeminal nerve during pituitary resection. The control group was defined as patients received pituitary adenomas resection without intraoperative TCR. The case and control groups were matched according to age, sex, and mostly closed date of surgery at the ratio of 1∶3. The incidence of postoperative cardiac adverse events, arrhythmia and hypertension/hypotension during recovery from anesthesia, postoperative pituitary insufficiency, electrolyte disorder, length of hospitalization stay, length of intensive care unit (ICU) stay, and hospitalization cost were observed in the two groups. The differences between the two groups were compared, and the risk factors for predicting TCR were predicted by univariate and multivariate logistic regression. Results A total of 22 patients (0.62%) met the TCR definition criteria. Compared with the control group, the case group had larger tumor diameter [(28.6±10.9) mm vs (20.5±9.0) mm, P=0.001], more invasive tumors (86.4% vs 56.1%, P=0.011), longer surgical duration [180 (121.5, 223.8) min vs 107 (69.5, 184.3) min, P=0.008], and a low total resection rate (45.5% vs 72.7%, P=0.022). Multivariate logistic analysis showed that invasive tumor was an independent risk factor for TCR in pituitary tumor surgery [odds ratio (OR)=5.85, 95%CI 1.35‒25.23, P=0.018]. The incidence of cardiac events and postoperative arrhythmia in the case group was higher than that in the control group (13.6% vs 0, P=0.014; 40.9% vs 16.7%, P=0.049) during recovery from anesthesia. The length of ICU stay [2.0(1.25, 2.00) d vs 0(0,0), P=0.014] and hospitalization cost (44 100 yuan vs 32 200 yuan, P=0.016) in the case group was higher than that in the control group . No statistical difference was found in other indicators between the two groups (P>0.05). Conclusions Invasive tumor is an independent risk factor for TCR during pituitary tumor resection.