Few studies have evaluated the presence of hepatic or peritoneal metastasis as a prognostic factor in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). This study aimed to elucidate the prognostic value of the initial metastatic, extrahepatic, or hepatic site in patients with metastatic PDAC. Between January 2007 and December 2013, the medical records of 343 patients with metastatic PDAC treated at Seoul National University Bundang Hospital were retrospectively reviewed. Patients were classified as having extrahepatic metastasis alone (EH), hepatic metastasis alone (LV), and both hepatic and extrahepatic metastasis (BOTH). The median age was 67 years; 207 patients were men. Patients were classified as having EH (111 patients), LV (106), and BOTH (126). Totally, 212 patients underwent chemotherapy with a FOLFIRINOX (23 patients) or gemcitabine-based regimen (189). On multivariate analysis, an ECOG score ≥2 (hazard ratio [HR]: 3.2, 95% confidence interval [CI]: 2.2-4.5), albumin < 35 g/L (HR: 1.6, 95% CI: 1.1-2.3), C-reactive protein > 10 mg/L (HR: 2.3, 95% CI: 1.6-3.2), neutrophil-lymphocyte ratio > 5 (HR: 1.4, 95% CI: 1.0-2.0), no chemotherapy (HR: 2.0, 95% CI: 1.0-4.1), and metastatic site (LV, HR: 2.1, 95% CI: 1.4-3.1; BOTH, HR: 2.2, 95% CI: 1.6-3.2) were significantly associated with shorter overall survival (OS). Considering the initial metastatic site, the median OS of patients with EH, LV, and BOTH were 7.5 (95% CI: 6.3-8.8), 4.8 (95% CI: 4.1-5.5), and 2.4 (95% CI: 1.9-2.9) months, respectively. The initial metastatic site is significantly and independently associated with OS in patients with metastatic PDAC, serving as an effective prognostic factor.