Background Accurate and non-invasive diagnosis of pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) can avoid unnecessary puncture and surgery. This study aimed to develop a deep learning radiomics (DLR) model based on contrast-enhanced ultrasound (CEUS) images to assist radiologists in identifying PDAC and CP. Methods Patients with PDAC or CP were retrospectively enrolled from three hospitals. Detailed clinicopathological data were collected for each patient. Diagnoses were confirmed pathologically using biopsy or surgery in all patients. We developed an end-to-end DLR model for diagnosing PDAC and CP using CEUS images. To verify the clinical application value of the DLR model, two rounds of reader studies were performed. Results A total of 558 patients with pancreatic lesions were enrolled and were split into the training cohort (n=351), internal validation cohort (n=109), and external validation cohorts 1 (n=50) and 2 (n=48). The DLR model achieved an area under curve (AUC) of 0.986 (95% CI 0.975-0.994), 0.978 (95% CI 0.950-0.996), 0.967 (95% CI 0.917-1.000), and 0.953 (95% CI 0.877-1.000) in the training, internal validation, and external validation cohorts 1 and 2, respectively. The sensitivity and specificity of the DLR model were higher than or comparable to the diagnoses of the five radiologists in the three validation cohorts. With the aid of the DLR model, the diagnostic sensitivity of all radiologists was further improved at the expense of a small or no decrease in specificity in the three validation cohorts. Conclusions The findings of this study suggest that our DLR model can be used as an effective tool to assist radiologists in the diagnosis of PDAC and CP.