〔Abstract〕 Abstract Objective To investigate the value of decreased carbohydrate antigen 19-9 (CA19-9) kinetics in pre- dicting short-term outcomes and determining prognosis among advanced biliary or pancreatic cancer patients receiv- ing first- or second-line therapy in the real world . Methods Eighty-nine patients were retrospectively collected with advanced biliary or pancreatic cancer , especially on the CA19-9 dynamics and decline rates at different time points . This study evaluated the association of CA19-9 changes with clinicopathological features , short-term re- sponse to antitumor therapy , and survival outcomes . Results The enrolled patients recorded baseline CA19-9 lev- els ranging from 1 . 20 to 65 706. 40 U/ml , with a median of 303 . 11 U/ml . There was no statistical correlation be- tween baseline CA19-9 levels and gender , age , body mass index , primary tumor site , hepatic metastases , pulmo- nary metastases , lymph node metastases , peritoneal metastases , performance status , treatment lines , and combina- tions of drug types . Baseline CA19-9 levels were not associated with systemic immunoinflammatory index , prognos- tic nutritional index , and total bilirubin . A 25% or 50% decrease in CA19-9 after 2 - 3 therapy courses indicated short-term efficacy in reaching tumor objective remission or disease control . Both combinations of multiple drug types and a 25% decline in CA19-9 after one course of treatment were independent prognostic factors that affected the longer progression-free survival of patients receiving first or second line of treatment. Conclusion Decreased CA19-9 kinetics has specific values in predicting the efficacy and prognosis of advanced biliary or pancreatic cancer.