Background Pancreatoduodenectomy is an extensive procedure with a very high risk of complications. Appropriate intraoperative fluid therapy is a subject of ongoing debate. The aim of this retrospective study was to analyze the relationship between selected preoperative parameters, intraoperative fluid therapy, and catecholamines administration during pancreatoduodenectomy. Material/Methods : From 2011 through 2017, among pancreatoduodenectomies performed at a single university hospital, 192 patients met the inclusion criteria of the study: 105 (54.7%) males and 87 (45.3%) females with a mean age of 60.06 (±11.63) years. Correlations were assessed between sex, age, body mass index (BMI), selected comorbidities, surgery duration, American Society of Anesthesiologists (ASA) Physical Status (PS) scale, preoperative endoscopic retrograde cholangiopancreatography (ERCP) and intraoperative catecholamine administration, intraoperative fluid supply, red blood cell (RBC) concentrate and fresh frozen plasma (FFP) supply, blood loss, and diuresis. Results A need for catecholamines has been shown to be more frequent in smokers ( P =0.01), patients with cardiovascular comorbidities ( P =0.037), high ASA PS scores ( P =0.003), and preoperative ERCP ( P =0.011). The need for intraoperative transfusion of RBC concentrate was more frequent in smokers ( P =0.005). Surgical time was significantly longer in males ( P =0.014). Among females, liberal intraoperative fluid therapy (>7.9 ml/kg/h) was more frequent in patients with thyroid comorbidities ( P =0.003). Conclusions The findings of this retrospective study demonstrate the influence of comorbidities, ASA PS class, and catecholamine use on fluid therapy during pancreatoduodenectomy.