ObjectiveTo systematically review the diagnostic value between serum human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) for endometrial cancer (EC). MethodsWe electronically searched databases including PubMed, The Cochrane Library, Web of Science, ScienceDirect, EBSCO, CNKI and VIP to collect diagnostic accuracy studies of serum HE4 and/or CA125 versus golden standard (pathology) for EC from inception to August 2014. Two reviewers independently screened literature, extracted data and assessed the risk bias of included studies by QUADAS-2 tool. Then, meta-analysis was performed by Meta-Disc 1.4 software. ResultsA total of 20 studies involving 4 351 participants were included. The results of meta-analysis showed that:the pooled sensitivity (Sen), specificity (Spe), positive likelihood ratio (+LR), and negative likelihood ratio (-LR), and diagnostic odds ratio (DOR) of HE4 in the diagnosis of EC were 0.56 (95%CI 0.54 to 0.58), 0.89 (95%CI 0.88 to 0.90), 6.19 (95%CI 4.31 to 8.88), 0.49 (95%CI 0.44 to 0.56), and 14.27 (95%CI 9.50 to 21.42), respectively. The area under the curve (AUC) of SROC was 0.855 9. The pooled Sen, Spe, +LR,-LR, and DOR of CA125 in the diagnosis of EC were 0.33 (95%CI 0.31 to 0.34), 0.80 (95%CI 0.78 to 0.82), 2.07 (95%CI 1.45 to 2.95), 0.83 (95%CI 0.76 to 0.91), and 2.65 (95%CI 1.63 to 4.32), respectively. The SROC AUC was 0.657 5. ConclusionCompared with CA125, HE4 has higher diagnostic accuracy for EC. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.