ObjectivesTrefoil Factor Family protein 1 (TFF1) is secreted from mucus-producing cells. The relationship between TFF1 expression and clinical outcome in pancreatic ductal adenocarcinoma (PDAC) remains unknown. We aimed to evaluate the prognostic significance of TFF1 expression in PDAC. MethodsTFF1 expression was examined on paraffin-embedded sections from 91 patients with resected PDAC using immunohistochemistry. The relationships between TFF1 expression and clinicopathological features were analyzed. ResultsAmong 91 PDAC patients, 71 patients (79.7%) showed TFF1 expression in cancer cells. In a subgroup of 71 patients, TFF1 expression was predominantly observed in the central part of the tumor, whereas TFF1 expression in the invasion front was reduced in 33 patients (46.4%). A significant correlation between preserved TFF1 expression in the invasion front and lymph node metastasis was observed. Univariate survival analysis revealed that preserved TFF1 expression in the invasion front, positive lymphatic invasion, lymph node metastasis and R1 resection was a significant poor prognostic factor in TFF1-positive PDAC patients. ConclusionsTFF1 expression is frequently lost or decreased in the invasion front of human PDAC, and preserved TFF1 expression in the invasion front might predict poor survival in patients with PDAC.