Objectives The aim of this study was to assess the impact of clinically relevant postoperative pancreatic fistula (CR-POPF) on patient disease-specific survival and recurrence after curative distal pancreatectomy (DP) for pancreatic cancer. Design This was a retrospective case-control analysis. Methods We examined the data of adult patients with a diagnosis of pancreatic ductal adenocarcinoma (PDAC) of the body and tail of the pancreas undergoing curative DP, over a 10-year period in 12 European surgical departments, from a prospectively implemented database. Results Among the 382 included patients, 283 met the strict inclusion criteria; 139 were males (49.1%) and the median age of the entire population was 70 years (range 37–88). A total of 121 POPFs were observed (42.8%), 42 (14.9%) of which were CR-POPFs. The median follow-up period was 24 months (range 3–120). Although poorer in the POPF group, overall survival (OS) and disease-free survival (DFS) did not differ significantly between patients with and without CR-POPF ( p  = 0.224 and p  = 0.165, respectively). CR-POPF was not significantly associated with local or peritoneal recurrence ( p  = 0.559 and p  = 0.302, respectively). A smaller percentage of patients benefited from adjuvant chemotherapy after POPF (76.2% vs. 83.8%), but the difference was not significant ( p  = 0.228). Conclusions CR-POPF is a major complication after DP but it did not affect the postoperative therapeutic path or long-term oncologic outcomes. CR-POPF was not a predictive factor for disease recurrence and was not associated with an increased incidence of peritoneal or local relapse. Trial Registration ClinicalTrials.gov ID: NCT04348084