Worldwide, the surgical management of pancreas cancer using the Whipple procedure rarely results in long-term survival even though there is an R0 resection. This manuscript explores the use of hyperthermic intraperitoneal chemotherapy in the operating room to reduce local-regional progressive disease. Gemcitabine monotherapy administered in the operating room as hyperthermic intraperitoneal chemotherapy (HIPEC) is supported by pharmacologic data. The exposure as measured pharmacologically by the area under the curve (AUC) of intraperitoneal concentration times time, divided by plasma concentration times time is 200-500. Data suggests that improved local control with HIPEC with gemcitabine may facilitate an improvement in pancreas cancer treatment that leads the way to more successful strategies with systemic chemotherapy.