Background and objective Pancreatic cancer tumors are difficult to access for biopsy. The use of coaxial needles during ultrasound (US)-guided coarse needle biopsy (CNB) may help to improve specimen collection yields and avoid tissue damage. In this retrospective study, the safety, efficacy, and clinical benefits of US-guided percutaneous coaxial CNB of pancreatic masses were evaluated and compared to those of non-coaxial CNB. Methods A total sample of 220 biopsies performed from August 2015 to August 2019 were analyzed, including 114 performed with a coaxial needle (17-gauge coaxial coarse needle combined with an 18-gauge coarse biopsy needle) and 106 performed with a non-coaxial needle (18-gauge coarse biopsy needle without a coaxial sheath). The coaxial CNB group was stratified by lesion location to further evaluate the applicability of coaxial core needles. The satisfactory specimen rate, diagnostic efficiency, operating time, and complication rate were compared statistically between groups and subgroups. Results Compared to the non-coaxial CNB group, the coaxial CNB group had a greater satisfactory specimen rate (98.3% vs. 92.3%;p = 0.048), a lesser mean operating time (8.9 +/- 3.27 min vs. 16.8 +/- 5.77 min;p < 0.001), and a lower complication rate (2.6% vs. 9.6%,p =0 .04). A better diagnostic efficiency was obtained for coaxial CNBs in the head of pancreas (98.7%) than in the body or tail of the pancreas (90%,p = 0.047). Conclusion For pancreatic masses, coaxial CNB can yield a higher satisfactory sample rate, lower complication rate, and shorter operating time than non-coaxial biopsy. US-guided percutaneous coaxial CNB is a safe and efficient puncture technique for pancreatic lesion diagnosis.