Objective To evaluate the efficacy of endoscopic photodynamic therapy (PDT) combined with biliary stenting on treatment of patients with extrahepatic cholangiocarcinoma or ampullary carcinoma. Methods Data of 60 patients with extrahepatic cholangiocarcinoma or ampullary carcinoma were collected in Eastern Hepatobiliary Hospital from September 2013 to December 2016, and patients were divided into stent group (n=36, undergone endoscopic biliary stenting only) and PDT group (n=24, undergone endoscopic PDT combined with biliary stenting). The clinical success rate, adverse events incidence, stent patency time and overall survival time were analyzed. Results No significant differences were found on baseline data between the stent group and PDT group (all P>0.05). No significant difference was found between the two groups in clinical success rate [94.4% (34/36) VS 95.8% (23/24), χ2=0.060, P=1.000], and early adverse events incidence [41.7% (15/36) VS 62.5% (15/24), χ2=2.50, P=0.187]. The Karnofsky performance score of the first, third and sixth month after operation in the PDT group were significantly higher than those in the stent group (all P<0.001). The median patency time of stent was 102.0 d (95%CI: 73.9-130.1 d) in the stent group, and 119.0 d (95%CI: 96.8-141.2 d) in the PDT group (P=0. 634). However, the median overall survival time was longer in the PDT group (327.0 d, 95%CI: 215.9-438.1 d) than that in the stent group (162.0 d, 95%CI: 125.0-199.0 d, P=0.006). Cox regression analysis showed that PDT was associated with a longer survival (P=0.012), while distal cholangiocarcinoma (P=0.016) and higher TNM staging (P=0.001) were associated with a shorter survival. Conclusion PDT with biliary stenting results in a longer survival and a better quality of life than the stenting therapy alone in patients with extrahepatic cholangiocarcinoma or ampullary carcinoma. PDT, location of lesions and TNM staging are independent prognostic factors for the survival of patients.