Malignant ascites is common in metastatic pancreatic cancer (mPC) and its management still remains a clinical challenge. Early identification of patients at risk for ascites development may support and guide treatment decisions. Data of patients treated for mPC at the Medical University of Vienna between 2010 and 2019 were collected by retrospective chart review. Ascites was defined as clinically relevant accumulation of intraperitoneal fluid diagnosed by ultrasound or computer tomography scan of the abdomen. We investigated the association between general risk factors, metastatic sites, liver function, systemic inflammation as well as portal vein obstruction (PVO) and ascites development. Among 581 patients with mPC included in this study, 122 (21.0%) developed ascites after a median of 8.7 months after diagnosis of metastatic disease. The occurrence of ascites led to an 8.9-fold increased risk of death [confidence interval (CI) 7.2-11, P < 0.001] with a median overall survival of 1 month thereafter. Clinical risk factors for ascites were male sex [hazard ratio (HR) 1.71, CI 1.00-2.90, P= 0.048], peritoneal carcinomatosis (HR 6.79, CI 4.09-11.3, P < 0.001), liver metastases (HR 2.16, CI 1.19-3.91, P= 0.011), an albumin-bilirubin (ALBI) score grade 3 (HR 6.79, CI 2.11-21.8, P= 0.001), PVO (HR 2.28, CI 1.15-4.52, P= 0.019), and an elevated C-reactive protein (CRP) (HR 4.19, CI 1.58-11.1, P= 0.004). Survival after diagnosis of ascites is very limited in mPC patients. Male sex, liver and peritoneal metastases, impaired liver function, PVO, as well as systemic inflammation were identified as independent risk factors for ascites development in this uniquely large real-life patient cohort.