Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest solid tumors, with five-year survival rates rarely exceeding 10%. Tumor location has been proposed as a prognostic factor, but prior studies have yielded inconsistent results due to methodological heterogeneity. Using the TriNetX Global Collaborative Network, we compared outcomes of resected PDAC in the head (pancreaticoduodenectomy) versus the body/tail (distal pancreatectomy). To capture definitive therapy, surgeries performed 30-365 days after diagnosis were included. One-to-one propensity score matching balanced demographics, comorbidities, and tumor stage. After matching, 2306 patients were analyzed. Thirty-day mortality was higher in head tumors (2.3% vs. 0.9%; HR 2.67, p < 0.001), with increased risk of sepsis, while other complications were similar. Long-term mortality remained greater for head tumors (39.8% vs. 31.6%), with shorter median survival (1131 vs. 2020 days). These findings suggest that tumor location is an independent, clinically meaningful prognostic factor after resection and support location-specific strategies.
