Esophagogastroduodenoscopy (EGD) referrals for symptoms of abdominal pain are common. Current guidelines for dyspepsia recommend biopsies of gastric mucosa for Helicobacter pylori in all patients referred for EGD. Our study aimed to determine the clinical yield and cost-effectiveness of gastric and duodenal biopsy in EGDs performed for abdominal pain. Three hundred and ninety-one outpatient EGDs performed at a single academic tertiary care center were studied. For each procedure, endoscopic as well as pathologic findings from the stomach and duodenum were then recorded. Charge of biopsy was calculated using the increased charges for professional fees, forceps, and pathology fees when a biopsy was performed. Gastric biopsies were obtained on 304 EGDs performed with 13 (4.2%) patients diagnosed with H. pylori. In patients with abnormal gastric mucosa on EGD, 11 of 167 (6.5%) were positive for H. pylori compared to 2 of 137 (1.4%) with normal appearing mucosa (p=0.02). Charge per diagnosis of H. pylori for normal mucosa was calculated to be $43,073. Duodenal biopsies were performed in 263 cases. Celiac disease was diagnosed in 4 of 263 cases (1.5%). Of patients with abnormal duodenal mucosa on EGD, 1 of 36 (2.7%) were positive for celiac disease compared to 3 of 227 (1.3%) with normal mucosa (p=0.57). Charge per diagnosis of celiac disease for normal mucosa was calculated to be $47,580. Routine biopsy during EGD for symptoms of abdominal pain has low yield with high costs. Practice of routine biopsies of normal appearing tissue and the present guidelines should be reconsidered in the investigation of abdominal pain with EGD.