Postoperative pancreatic fistula (POPF) significantly hampers chemotherapy delivery in pancreatic cancer patients.

• 16.8% of patients developed POPF, leading to lower chemotherapy administration rates at 72.1% and a median delay of 56 days.
• Independent predictors for chemotherapy omission include age ≥ 70 (odds ratio 2.48) and chronic renal failure (odds ratio 4.55) when POPF occurs.
• In patients without POPF, factors like venous contact and tumor size also influence chemotherapy delivery.

Assessing POPF risk preoperatively can refine patient selection for surgery and enhance treatment outcomes.