Background Palliative therapies for unresectable cholangiocarcinoma such as stent, radiotherapy and chemotherapy have generally been disappointing. Therefore, it is necessary to find a new approach to fighting the disease. Several published clinical trials have reported the therapeutic effect of photodynamic therapy (PDT) for unresectable cholangiocarcinoma. Objective To assess the safety and efficacy of photodynamic therapy for patients with unresectable cholangiocarcinoma. Methods Relevant studies were retrieved from the Medline, Current Contents, Embase, and Cochrane Library databases. Inclusion of papers was determined by using a predetermined protocol; independent assessments and the final consensus decision were performed by two independent reviewers. Acceptable study designs included randomized controlled trials (RCTs), controlled clinical trials (CCTs), case studies, and case reports. Twenty studies met the inclusion criteria, and were tabulated and critically appraised in terms of characteristics, methods, outcomes, and complications. Results Twenty studies were included. The quality of the available evidence was low to moderate with the majority of studies being uncontrolled before and after design and thus limited by the retrospective nature of much of the available data. After PDT, it is reported that bilirubin serum levels declined, quality of life improved and survival time increased in most of the patients. At the same time, there were few complications. Conclusions Based on currently available evidence, PDT was safe and effective for patients with inoperable cholangiocarcinoma.