BackgroundsPercutaneous ultrasound (US) and endoscopic ultrasound (EUS)-guided pancreatic biopsies are widely accepted in the diagnosis of pancreatic diseases. Studies comparing the diagnostic performance of US- and EUS-guided pancreatic biopsies are lacking. This study aimed to evaluate and compare the diagnostic yields of US- and EUS-guided pancreatic biopsies and identify the risk factors for inconclusive biopsies. MethodsOf the 1074 solid pancreatic lesions diagnosed from January 2017 to February 2021 in our center, 275 underwent EUS-guided fine needle aspiration (EUS-FNA), and 799 underwent US-guided core needle biopsy (US-CNB/FNA). The outcomes were inconclusive pathological biopsy, diagnostic accuracy and the need for repeat biopsy. All of the included factors and diagnostic performances of both US-CNB/FNA and EUS-FNA were compared, and the independent predictors for the study outcomes were identified. ResultsThe diagnostic accuracy was 89.8% for EUS-FNA and 95.2% for US-CNB/FNA (P = 0.001). Biopsy under EUS guidance [odds ratio (OR) = 1.808, 95% confidence interval (CI): 1.083-3.019; P = 0.024], lesion size < 2 cm (OR = 2.069, 95% CI: 1.145-3.737; P = 0.016), hypoechoic appearance (OR = 0.274, 95% CI: 0.097-0.775; P = 0.015) and non-pancreatic ductal adenocarcinoma carcinoma (PDAC) diagnosis (OR = 2.637, 95% CI: 1.563-4.449; P < 0.001) were identified as factors associated with inconclusive pathological biopsy. Hypoechoic appearance (OR = 0.236, 95% CI: 0.064-0.869; P = 0.030), lesions in the uncinate process of the pancreas (OR = 3.506, 95% CI: 1.831-6.713; P < 0.001) and non-PDAC diagnosis (OR = 2.622, 95% CI: 1.278-5.377; P = 0.009) were independent predictors for repeat biopsy. Biopsy under EUS guidance (OR = 2.024, 95% CI: 1.195-3.429; P = 0.009), lesions in the uncinate process of the pancreas (OR = 1.776, 95% CI: 1.014-3.108; P = 0.044) and hypoechoic appearance (OR = 0.127, 95% CI: 0.047-0.347; P < 0.001) were associated with diagnostic accuracy. ConclusionsIn conclusion, both percutaneous US- and EUS-guided biopsies of solid pancreatic lesions are safe and effective; though the diagnostic accuracy of EUS-FNA is inferior to US-CNB/FNA. A tailored pancreatic biopsy should be considered a part of the management algorithm for the diagnosis of solid pancreatic disease.