Introduction: The use of neoadjuvant therapy (NAT) for pancreatic cancer is increasing, although its impact on postoperative pancreatic fistula (POPF) is variably reported. This systematic review and meta-analysis aimed to assess the impact of NAT on POPF. Methods: A systematic literature search until October 2019 identified studies reporting POPF following NAT (radiotherapy, chemotherapy or chemoradiotherapy) vs. upfront resection. The primary outcome was overall POPF. Secondary outcomes included Grade B/C POPF, delayed gastric emptying (DGE), postoperative pancreatic haemorrhage (PPH), and overall and major complications. Results: The search identified 24 studies: pancreaticoduodenectomy (PD), 19 studies (n=19,893); distal pancreatectomy (DP), 5 studies (n=477). Local staging was reported in 17 studies, with borderline resectable and locally advanced disease comprising 6% (0 - 100%) and 1% (0 - 33%) of the population, respectively. For PD, any NAT was significantly associated with lower rates of overall POPF (OR: 0.57, p< 0.001) and Grade B/C POPF (OR: 0.55, p< 0.001). In DP, NAT was not associated with significantly lower rates of overall or Grade B/C POPF. Conclusion: NAT is associated with significantly lower rates of POPF after PD but not after DP. Further studies are required to determine whether NAT should be added to POPF risk calculators.