Objective To analyze the risk factors of post-operative complications of endoscopic retrograde cholangiopancreatography (ERCP) in patients with liver cirrhosis, and to establish a simple and practical scoring system. Methods We retrospectively analyzed the clinicopathological data of 223 patients with liver cirrhosis who underwent ERCP in Changhai Hospital of Second Military Medical University from Jan. 2009 to Dec. 2015. The univariate analysis and logistic multivariate regression analysis were used to study the effects of pre-operative status, lab parameters and operation performance on post-operative complications. After screening for independent risk factors and transforming the continuous variables into categorical variables, we assigned the scores according to the β value of each independent risk factor, established a new scoring system to predict the occurrence of post-operative omplications, and then drew the receiver operating characteristic (ROC) curve to assess its predicting efficacy for complications. Results Multivariate regression analysis showed that total bilirubin (TBIL) was an independent risk factor for post-operative complications with an OR of 1.003 (95%CI 1.001, 1.005), and albumin (ALB) as a protective factor with an OR of 0.935 (95%CI 0.879, 0.994). The scoring system established according the two factors was as follows:TBIL ≤ 31.4 μmol/L for 0 point, 31.5-102.5 μmol/L for one point, ≥ 102.6 μmol/L for two points; ALB ≥ 31 g/L for 0 point, ≤ 30 g/L for one point. The area under ROC curve (AUC) of the new scoring system was 0.689, which was similar to the Child-Pugh classification (0.700) and the model for end-stage liver disease (MELD) score (0.692) by ROC analysis. All patients were divided into two parts by 1.5 points according to the new scoring system (0-1 point was set as low-risk, and 2-3 points was high-risk). The sensitivity of the new scoring system was 89.4%, specificity was 41.1%, accuracy rate was 49.3%, the positive predictive value was 23.7%, and the negative predictive value was 95.0%. Conclusion The new scoring system for post-ERCP complications is easy-to-use and can be used to identify patients at high-risk.