BACKGROUND: CA-125 is a clinical biomarker with predictive effect on the prognosis of different cancers. Numerous clinical trials have been conducted to investigate the possibility of using the pretreatment level of CA-125 to predict the prognosis of epithelial ovarian cancer (EOC). However, its value in predicting prognosis remains controversial. The purpose of this meta-analysis was to assess the predictive value of pretreatment CA-125 levels for prognosis in EOC patients. METHODS: We searched the EMBASE, Cochrane library, PubMed and Web of Science databases for studies published up to 3 December 2021, according to specific inclusion and exclusion criteria. The clinical studies that were included investigated the relationship between pretreatment CA-125 levels and ovarian cancer prognosis. Combined hazard ratios (HR) of overall survival (OS) and progression-free survival (PFS) reported in the studies were compared and analyzed using fixed-effects/random-effects models. Sensitivity analysis was used to assess study stability, while Egger's and Begg's tests were used to assess publication bias. RESULTS: This meta-analysis included 23 studies published in 2004 - 2021 with a total of 10,594 EOC patients. Comprehensive analysis demonstrated that the serum level of CA-125 before treatment was significantly correlated with overall survival (OS: HR=1.62, 95%CI=1.270-2.060, p<0.001) and progression-free survival (PFS: HR=1.59, PFS: HR=1.59, 95%CI=1.44~1.76, p<0.001). After comparing data from different FIGO stages and treatments, we discovered that a high pre-treatment serum CA-125 level was associated with a low survival rate. CONCLUSION: According to the results of this study, a higher pre-treatment serum CA-125 level is associated with poor survival outcomes, which can be utilized to predict the prognosis of EOC patients. Pre-treatment serum CA-125 level might provide reliable basis for predicting the risk of EOC disease progression. This study is registered with the International Prospective Register of Systematic Reviews (CRD42022300545). SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=300545, identifier [CRD42022300545].