Background and Aims A side-port needle has been developed to improve diagnostic accuracy by obtaining more cellular material during EUS-guided FNA (EUS-FNA). We compared the accuracy rate of histology and the quality of histologic specimens from 22-gauge (G) side-port and standard needles for EUS-FNA of a solid pancreatic mass in a multicenter, prospective, randomized control trial. Methods Between January 2013 and September 2013, 160 consecutive patients with a suspected solid pancreatic mass at 5 tertiary referral centers were enrolled. Patients were randomized to the 22G side-port needle or 22G standard needle group. The primary endpoint was the diagnostic accuracy of histology. Secondary endpoints were the quality of the histologic specimen (quantity of tissue, degree of GI contamination, and amount of blood). Results An analysis of 154 patients (side-port, 76, vs standard, 78) was performed. Six patients were excluded because of no pancreatic mass on EUS. There was no significant difference in the rate of diagnostic accuracy of histology (side-port, 87% 66/76, vs standard, 82% 64/78; P  = .51). Samples that enabled histologic interpretation were obtained in 64% (47/73) and 43% (33/77) of patients from the side-port and standard groups, respectively ( P  = .009). No significant difference was seen in the degree of GI contamination and amount of blood between groups. Conclusions There was no significant difference in the accuracy rate of histology between needle types. The side-port needle was superior to the standard needle in terms of obtaining samples that enabled histologic interpretation.