Objective To explore the diagnostic value of the imaging features of mural nodules in differentiating benign from malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Methods In this retrospective study, we analyzed the pathology and imaging data of 112 patients with IPMNs in Changhai Hospital from Jan. 2012 to Jun. 2016. All patients underwent computed tomography (CT) and magnetic resonance imaging (MRI), and the mural nodule imaging features were observed and recorded by two resident physicians. The size, location, amount, margin and enhancement of the mural nodules were compared and analyzed in benign and malignant IPMNs. Finally, a receiver operating characteristic (ROC) curve was drawn and the area under curve (AUC) was calculated to evaluate the diagnostic value of the size, amount and margin of the mural nodules observed by imaging in differentiation of malignant and benign IPMNs, and to determine the best cut-off value, sensitivity, specificity and accuracy of the size. Results Sixty-one patients with definite mural nodules confirmed by pathology after surgery and imaging examination were included in this study; pathological analysis showed 36 patients having benign IPMNs and 25 having malignant, with main duct in 15 patients, branch duct in 13, and mixed type in 33. The malignant IPMNs mainly occurred in main duct and mixed type (P=0.01). The size of the mural nodules could be used to distinguish benign from malignant IPMNs (P<0.01), and the best cut-off value was 1.35 cm; the AUC was 74.7%, and the sensitivity, specificity and accuracy were 56.0%, 91.7% and 77.5%, respectively. Multiple mural nodules (P=0.02) and ill-defined margins (P<0.01) could be an imaging features for distinguishing benign from malignant IPMNs, and the AUC was 64.2% and 72.1%, respectively. The mural nodules of all patietns showed a progressive enhancement, which was not useful for differentiation. Conclusion The imaging features of the mural nodules are valuable for differentiation between benign from malignant IPMNs of the pancreas, and it is of clinical value for pre-operative evaluation and follow-up.