Objective To explore the diagnostic value of endoscopic retrograde cholangiopancreatography(ERCP)related techniques combined with serum CEA and CA199 for obstruction of bile duct.Methods A total of 155 patients with bile duct obstruction who were admitted to our hospital between June 2010 and December 2013 were included in this study. Serum tumor markers (CEA and CA199)were tested before ERCP. Bile cytology,bile duct brush cytology and bile duct biopsy were conducted during ERCP. We expressed the diagnostic value as the sensitivity,specificity,positive predictive value,negative predictive value,accuracy,Youden index and Kappa value.Results Of the 155 patients, 56 had benign biliary obstruction and 99 had malignant biliary obstruction.Significant differences were found for serum CEA and CA199 between benign and malignant obstruction group patients [2.55(1.70-3.11)ng/mL vs. 3.26(1.95-7.00)ng/mL,P=0.002;46.91(13.24-115.90)U/mL vs 258.20(74.80-1000.00)U/mL,P=0.000].The 3 ng/mL and 150 U/mL were selected as the cutoff values for CEA and CA199,respectively.Based on the sensitivity and specificity,CA199 had a greater significance than CEA for bile duct obstruction. Bile duct brush cytology had a greater significance than bile cytology and bile duct biopsy.For bile cytology,bile duct brush cytology and bile duct biopsy,the sensitivity was 23.0%,72.0% and 69.1%,respectively,the specificity all were 100%,the positive predictive values all were 100%,the negative predictive values were 16.3%,34.4%,10.5%,the accuracy was 33.0%,75.6%,70.2%,the Youden index was 0.23,0.72,0.69,and the Kappa values were 0.072,0.397,0.136,respectively.Combined with one and more ERCP-related techniques,the combination of bile duct brush cytology with bile duct biopsy had the greatest significance than others.The sensitivity,specificity,positive predictive value,negative predictive value,accuracy,Youden index,and Kappa value were 82.2%,100%,100%,40.7%,84.2%,0.822 and 0.502,respectively. For patients with serum CEA≥3ng/mL or CA199≥150U/mL,combined with bile duct brush cytology with bile duct biopsy,the sensitivity was 89.4%,83.0%,specificity all were 100%,positive predictive values all were 100%,negative predictive values were 50.0%,35.7%,accuracy was 90.4%,84.5%,Youden index were 0.894,0.830,and Kappa values were 0.618,0.457,respectively.The diagnostic values were increased.Conclusion The combination of bile duct brush cytology,bile duct biopsy during ERCP,and serum CEA,CA199 levels before ERCP had definite value for the diagnosis of bile duct obstruction.Serum CEA≥3 ng/mL could be used for the selection of patients with high risk before ERCP,bile duct brush cytology combined with bile duct biopsy was recommended for patients with bile duct obstruction and baseline serum CEA≥3 ng/mL.