BackgroundCT prediction of resectability and prognosis following neoadjuvant treatment (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC) remains challenging. This study aims to determine whether addition of18F-fluorodeoxyglucose (FDG) postiron emission tomography (PET)/MRI and carbohydrate antigen (CA) 19–9 to contrast-enhanced CT (CECT) can improve accuracy of predicting resectability compared to CECT alone and predict prognosis in PDAC patients after NAT.MethodsIn this retrospective study, 120 PDAC patients (65 women; mean age, 66.7 years [standard deviation, 8.4]) underwent CECT, PET/MRI, and CA 19–9 examinations after NAT between January 2013 and June 2021. Three board-certified radiologists independently rated the overall resectability on a 5-point scale (score 5, definitely resectable) in three sessions (session 1, CECT; 2, CECT plus PET/MRI─no FDG avidity and no diffusion restriction at tumor-vessel contact indicated modification of CECT scores to ≥ 3; 3, CECT plus PET plus CA 19–9─no FDG avidity at tumor-vessel contact and normalized CA 19–9 indicated modification of CECT scores to ≥ 3). Jackknife free-response receiver operating characteristic method and generalized estimating equations were used to compare pooled area under the curve (AUC), sensitivity, and specificity of three sessions. Predictors for recurrence-free survival (RFS) were assessed using Cox regression analyses.ResultsEach session showed different pooled AUC (session 1 vs. 2 vs. 3, 0.853 vs. 0.873 vs. 0.874,p= 0.026), sensitivity (66.2% [137/207] vs. 86.0% [178/207] vs. 84.5% [175/207],p< 0.001) and specificity (67.3% [103/153] vs. 58.8% [90/153] vs. 60.1% [92/153],p= 0.048). According to pairwise comparison, specificity of CECT plus PET/MRI was lower than that of CECT alone (adjustedp= 0.042), while there was no significant difference in specificity between CECT alone and CECT plus PET plus CA 19–9 (adjustedp= 0.081). Twenty-eight of 69 patients (40.6%) with R0 resection experienced tumor recurrence (mean follow-up, 18.0 months). FDG avidity at tumor-vessel contact on post-NAT PET (HR = 4.37,p= 0.033) and pathologically confirmed vascular invasion (HR = 5.36,p= 0.004) predicted RFS.ConclusionCombination of CECT, PET and CA 19–9 increased area under the curve and sensitivity for determining resectability, compared to CECT alone, without compromising the specificity. Furthermore,18F-FDG avidity at tumor-vessel contact on post-NAT PET predicted RFS.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40644-023-00565-8.