Objective To assess the effectiveness and safety of reptilase in the treatment of bleeding due to internal diseases. Methods The Cochrane Library, MEDLINE, VIP, and CNKI were searched. The quality of included studies was evaluated and meta-analysis was performed for the results of homogeneous studies. Results Forty studies involving 2 879 participants related to a variety of internal diseases were included. All included studies were inadquate in reporting randomization, concealment of allocation and blinding. Meta-analysis based on included studies showed that reptilase could better alleviate bleeding compared with the control group in intrecranial encephalic hemorrhage （RD 0. 24, 95 % CI 0. 01 to 0.48）, hypertension induced intrecranbd hemorrhage （RD -0.20, 95% CI -0. 38 to -0. 03）, in hemostasis rate within 24 hours in hemoptysis （RD 0.41, 95% CI 0.17 to 0. 64）, in upper alimentary tract hemorrhage （ RD 0.39, 95% CI 0.03 to 0. 76 ）, in newborn upper alimentary tract hemorrhage （RD 0.32, 95% CI 0. 23 to 0.41 ）. Only one case of hypersensitivity occured in reptilase group. Conclusions Reptilase is an effective and safe hemostasia remedy for hemorrhage of internal diseases. Due to high risk of selection bias and detection bias of included studies, the evidence is not b enough to judge whether reptilase is better than other hemostatics. Our results suggest that further and larger-scale trials of the use of reptilase in the treatment of hemorrhages of internal diseases are needed.