Objective To retrospectively analyze the risk factors associated with biliary‑cardiac reflex under general anesthesia for endoscopic retrograde cholangiopancreatophraphy (ERCP). Methods There were totally 1 358 patients who underwent ERCP under general anesthesia. According to the presence of biliary‑cardiac reflex, 1 242 patients who met the selection criteria were enrolled and divided into two groups: a biliary‑cardiac reflex group (n=181) and a no biliary‑cardiac reflex group (n=1 061). Then, age, sex, timing of surgery, intubation, coronary heart disease, arrhythmia, allergy history, preoperative application of atropine, intraoperative application of 654‑2, ERCP history, operation time grade, ASA grade and endoscopic doctor were included for single factor analyze. The factors of P<0.05 in the single analysis were further included in the multicollinearity analysis and the multivariate Logistic multivariate regression analysis. Meanwhile, the incidence of biliary‑cardiac reflex when the nipple columnar balloon was expanded, the stone was removed, the duodenal papilla was intubated, and other periods. Results The incidence of biliary‑cardiac reflex in the 1 242 patients was 14.6% (n=181), where the incidence of biliary‑cardiac reflex was higher when the nipple columnar balloon was expanded and when the stone was removed than that when the duodenal papilla was intubated and other periods. The results of multicollinearity analysis showed that emergency surgery, coronary heart disease, arrhythmia, without history of ERCP, no preoperative application of atropine, no intraoperative application of 654‑2, and advanced age were no multicollinearity. The results of multivariate Logistic regression analysis showed that emergency surgery, arrhythmia, no history of ERCP, no preoperative use of atropine, no intraoperative use of 654‑2, and advanced age were independent risk factors for the occurrence of biliary‑cardiac reflex (P<0.05). Conclusions Emergency surgery, arrhythmia, no history of ERCP, no preoperative use of atropine, no intraoperative use of 654‑2, and advanced age were the independent risk factors for the occurrence of biliary‑cardiac reflex. Preoperative use of atropheric and the application of 654‑2 in surgery to inhibit intestinal peristalsis can effectively reduce the occurrence of biliary‑cardiac reflex. And the high biliary‑cardiac reflex is when the nipple columnar balloon was expanded and when the stone was removed.