(1) Background: Patients with pancreatic exocrine insufficiency (PEI) have an increased risk of malnutrition, which in turn increases morbidity and mortality and is frequent in pancreatic head cancer. This study aimed to analyze the utility of PEI measured using the stool elastase (SE) level to predict the prognosis of patients with pancreatic head cancer. (2) Methods: Patients who underwent pancreaticoduodenectomy for pancreatic cancer at our institution between 2011 and 2015 were included. Only patients with data on preoperative SE levels were analyzed. Patients were classified into low and high SE groups based on preoperative SE levels (low < 100 µg/g < high). (3) Results: The median preoperative SE level was 67.2 µg/g, and 84 of 143 (58.7%) patients were included in the low SE group. The two groups had significantly different overall survival (OS) and disease-free survival (DFS), and the low SE group had a worse prognosis. In multivariate analysis, SE level < 100 µg/g and lymph node metastasis were independent poor prognostic factors for OS and DFS. (4) Discussion: PEI measured using SE levels is an independent prognostic factor in patients with pancreatic head cancer undergoing pancreaticoduodenectomy. Since poor nutritional status may be related to prognosis in patients with low levels of stool elastase preoperatively, aggressive treatment may be required.