Background: Studies that correlated EUS features of chronic pancreatitis (CP) with histopathology are retrospective and only include patients with severe disease or calcific pancreatitis. Controversies regarding the significance of EUS features of noncalcific CP (NCCP) remain unresolved. Objective: To correlate EUS criteria for NCCP with histology from surgical specimens. Design: Prospective study. Setting: Tertiary referral center. Patients: All patients who underwent EUS for pancreaticobiliary indications and subsequent pancreatic surgery. Patients with calcific pancreatitis were excluded. Methods: Individual CP features on EUS were carefully documented with relation to different parts of the pancreas. Standard EUS criteria for CP were adopted. All patients underwent surgery within 2 months of EUS. A single pathologist blinded to EUS findings reviewed the specimens and graded fibrosis (total score, 12; ≥6 = unequivocal CP). A quantitative receiver operating characteristic (ROC) curve analysis was performed, and Spearman rank correlation coefficients were calculated. Main Outcome Measurements: Correlate EUS criteria for NCCP, with histology from surgical specimens. Results: Of the 42 patients evaluated, NCCP was diagnosed histologically in 21 patients (50%). None of the patients had CP diagnosis by CT. ROC curve analysis revealed that 4 or more EUS criteria provided the best sensitivity (90.5%), specificity (85.7%), and accuracy (88.1%) for diagnosing NCCP. Parenchymal EUS features that were significantly associated with histopathologic NCCP were foci (P < .0001), stranding (P < .001), and lobulations (P = .04); ductal features that were significantly associated with histopathologic NCCP were dilated (P < .0001) or irregular main pancreatic duct (P < .0001), side branches (P < .001), and hyperechoic duct margins (P = .03). There was a significant correlation between the number of EUS criteria and severity of NCCP on histology (r = 0.85; P < .0001). Limitations: Small number of patients. Conclusions: An excellent correlation exists between EUS and histologic findings of NCCP. © 2007 American Society for Gastrointestinal Endoscopy.