Sheng Zhao,1 Yanping Miao,2 Ruijun Wang,2 Haidong Guo,2 Feng Jin,2 Xiuling Guo,2 Tianyou Luo1 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Radiology, The First Affiliated Hospital of Inner Mongolia Medical University, Huhhot Inner Mongolia, People’s Republic of China Purpose: The purpose of this study was to assess the efficacy and toxicities of adding molecular targeted agents (MTAs) to first-line chemotherapy in the treatment of advanced biliary tract cancer (BTC). Methods: An extensive search for relevant clinical trials was conducted in electronic databases (PubMed, Web of Science, and Cochrane) and abstracts presented at meetings. Prospective randomized controlled trials (RCTs) reporting the efficacy and toxicity of chemotherapies with or without MTAs in advanced BTC were selected. The endpoints were overall survival (OS), progression-free survival (PFS), and grade 3 or 4 toxicities. The results were expressed as hazard ratio or relative risk (RR), with their corresponding 95% confidence intervals. Results: The final analysis included a total of 855 advanced BTC patients from six RCTs. Compared with chemotherapy alone, the combination of MTAs with chemotherapy significantly improved overall response rate (ORR) (RR 1.68, 95% confidence interval: 1.28–2.19, P