Non-ulcer dyspepsia (NUD) is a term used to define a set of symptoms that are believed to originate from the gastroduodenal region, and no underlying organic, systemic, or metabolic reason can be found. The majority of patients suffer from chronic symptoms although half of the patients report improvement in symptoms with time. The potential role exocrine pancreatic insufficiency in NUD patients has not been clarified yet. We aimed to identify exocrine pancreas function with pancreatic fecal elastase-1 in patients diagnosed with non-ulcer dyspepsia and no typical exocrine pancreatic insufficiency (EPI) symptoms. Thirty-five patients referred to gastroenterology clinics with NUD and 35 people with no dyspeptic symptoms as a control group were included in this prospective study. Non-ulcer dyspepsia patients were classified as group 1 and control subjects classified as group 2. Upper gastrointestinal endoscopies were performed in both groups. Assessment of exocrine pancreatic function was performed by measuring fecal elastase-1 concentration with a commercial ELISA kit using polyclonal antibodies (BioServ Diagnostics) in NUD patients compared to control subjects. Mean fecal elastase-1 levels were significantly lower in group 1 patients compared with group 2 (367.47 +/- 43.27; 502.48 +/- 50.94 respectively; p = 0.04). The percentage of the patients with EPI was significantly higher in group 1 (p = 0.02). Patients with NUD should be re-evaluated if they do not show satisfactory improvement with treatment. Exocrine pancreatic insufficiency was significantly higher in patients with NUD in our study. Evaluation for the presence of EPI can be a cost effective approach in management of refractory patients during the process of ruling out organic reasons.