© 2017 Wiley Periodicals, Inc. Background: Endoscopic ultrasound (EUS) fine needle aspiration (FNA) is an integral part in the diagnosis of pancreatic, intestinal and extra-intestinal masses or lesions. There is no clear data on the superiority of the core biopsy needle over standard 22-gauge needles. The aim of this study is to prospectively compare the cellularity yield of three commonly used 22-gauge FNA needles available in the US market. Methods: This is a prospective, randomized study comparing the cellularity yield of three commercially available EUS needles (two standard FNA needles and core biopsy needle). Two blinded pathologists evaluated the cytology specimens based on an already agreed upon cytology score. We included adult patients (18–80 years old) who presented to our endoscopy unit for FNA of pancreatic or extrapancreatic masses. Results: 109 patients (57 F, 52 M) were recruited to the study, 88 lesions were pancreatic lesions. 39 patients were recruited in the EZ Shot 2™ group, 36 in the Procore® group and 34 in the Expect™ group. The average cellularity score and the mean number of passes (SD) were not different between the three needles; P = 0.91 and P = 0.16, respectively. There was no difference between the three needles in obtaining an onsite diagnosis (P = 0.627) and no difference in reported adverse events between the three groups. Conclusion: The cellularity yields, the mean number of passes and reported adverse events were similar in the three compared 22-gauge needles. Diagn. Cytopathol. 2017;45:426–432. © 2017 Wiley Periodicals, Inc.