Background: Ascites and peritoneal metastases are major interruptive factors in sequential chemotherapy for advanced gastric cancer (AGC), although there are no established markers that predict ascites burden during treatment. Therefore, we aimed to clarify the association between serum CA125 and therapeutic efficacy for AGC treated with taxane plus ramucirumab (TAX/RAM). Methods: This multicenter retrospective study comprised AGC patients who received TAX/RAM in second or third line setting between Jun. 2015 to May 2019. Patient background and treatment outcome was assessed in CA125 elevated and non-elevated group before TAX/RAM (cut-off, 37 U/ml). The CA125 kinetics after chemotherapy was calculated based on baseline and first measure of CA125. Further, the association between early CA125 change and ascites burden during chemotherapy were evaluated based on optimal cut off value calculated receiver operating characteristic (ROC) curve analysis. Results: A total 73 patients from 5 hospitals were assessable. The proportion of poor PS, moderate/severe peritoneal effusion, low albumin was significantly larger in CA125 elevated group (n=31) than those in non-elevated group. The median value of CA125 before TAX/RAM was elevated according to ascites burden (none, 37.5 U/ml; mild, 57.9 U/ml; moderate/severe, 134.8 U/ml; p<0.001). The overall survival was significantly shorter in elevated group than that in non-elevated group (median, 8.2 vs. 14.6 months, p=0.0004). Baseline CA125 elevation and peritoneal metastasis were independent prognostic factors in multivariate analysis. After TAX/RAM, first-time measure of CA125 was performed in a median of day 28. The median change of CA125 was correlated with ascites response (CR/PR, -1.86%/day; SD, 0.28%/day; PD, 2.33 %/day, p<0.001). ROC curve analysis showed that the optimal cut-off value of CA125 kinetics for ascites progression was 0.0067%/day (specificity 74%, sensitivity 100%). The progression free survival in increased group was significantly shorter than that of non-increased group in patients with peritoneal dissemination (median, 2.5 vs 6.1 months, p=0.0008). Conclusions: The serum CA125 before TAX/RAM was associated with ascites burden. Further, early change of CA125 after TAX/RAM was associated with prognosis in AGC patients with peritoneal dissemination. CA125 monitoring may be biomarker in determining timing of treatment change.