Background EUS is an important modality for the diagnosis of pancreatic disease. An understanding of normal pancreatic ductal and parenchymal variation in asymptomatic individuals is essential to improve EUS accuracy. The primary aim of this study was to determine age-related pancreatic parenchymal and ductular changes identifiable on EUS in individuals with no history or symptoms of pancreaticobiliary disease. Secondary aims were to define demographic and clinical factors associated with identifiable pancreatic parenchymal and ductular changes, and to determine the main pancreatic-duct diameter and pancreatic-gland width according to age. Methods Patients referred for either upper endoscopy or EUS for an indication unrelated to pancreaticobiliary disease were prospectively enrolled. Patients were stratified by age (<40, 40-60, >60 years). Each patient was assessed for the presence of EUS findings for chronic pancreatitis. Logistic regression was used to identify factors associated with an abnormality. Results A total of 120 patients (63 men, 57 women; median age, 52 years, interquartile range [IQR] 40-61 years) were prospectively evaluated. At least one parenchymal and/or ductular abnormality was identified in 28% of the patients, with a trend of increasing abnormality with age: <40 years (23%), 40 to 60 years (25%), and >60 years (39%); p = 0.13. No patient had more than 3 abnormal EUS features. Hyperechoic stranding (n = 22) was the most common finding in all age groups. The odds for any abnormality in men (relative to women) was significantly higher (OR 2.9: 95% CI[1.2, 6.8], p = 0.01), with 38% of men and 18% of women having an abnormality. Smoking, low alcohol intake, body mass index, and endoscopic finding were not significantly associated with an abnormal EUS. The overall median pancreatic-gland width and main pancreatic duct diameter were 15 mm (IQR 6-25 mm) and 1.7 mm (IQR 0.9-4.3 mm), respectively. Conclusions The frequency of EUS abnormalities in patients without clinical evidence of chronic pancreatitis increases with age, particularly after 60 years of age. The threshold number of EUS criteria for the diagnosis of chronic pancreatitis is variable. However, the typically used standard of 3 or more criteria appears appropriate. A higher number of threshold criteria may be needed in males and to a lesser extent in patients over 40 years of age, which should be related to clinical history and other structural or functional studies. Ductal or parenchymal calculi, ductal narrowing, ductal dilatation, or more than 3 abnormalities appear to be more specific features for the EUS diagnosis of chronic pancreatitis at any age.