Background/AimsDifferentially diagnosing focal-type autoimmune pancreatitis (f-AIP) and pancreatic cancer (PC) is challenging. Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) may provide information for differentiating pancreatic masses. In this study, we evaluated the usefulness of CEH-EUS in differentiating f-AIP from PC.Methods : Data were collected prospectively and analyzed on patients who underwent CEH-EUS between May 2014 and May 2015. Eighty consecutive patients were diagnosed with f-AIP or PC. PC and f-AIP were compared for enhancement intensity, contrast agent distribution, and internal vasculature.Results : The study group comprised 53 PC patients and 27 f-AIP patients (17 with type-1 AIP [15 definite and two probable], two with probable type-2 AIP, and eight with AIP, not otherwise specified). Hyper- to iso-enhancement in the arterial phase (f-AIP, 89% vs PC, 13%; p<0.05), homogeneous contrast agent distribution (f-AIP, 81% vs PC, 17%; p<0.05), and absent irregular internal vessels (f-AIP, 85% vs PC, 30%; p<0.05) were observed more frequently in the f-AIP group. The combination of CEH-EUS and enhancement intensity, absent irregular internal vessels improved the specificity (94%) in differentiating f-AIP from PC.Conclusion : sCEH-EUS may be a useful noninvasive modality for differentially diagnosing f-AIP and PC. Combined CEH-EUS findings could improve the specificity of CEH-EUS in differentiating f-AIP from PC.