Background Background: Pre-operative neoadjuvant chemotherapy (NAC) is routinely used for pancreatic ductal adenocarcinoma (PDAC), however there are no validated tools for evaluating pathologic response in these patients. This study compared changes in imaging characteristics to determine if pathologic response after NAC can be predicted. Methods 36 patients with histologically confirmed PDAC, who underwent pancreaticoduodenectomy, with pre-operative NAC and pre and post therapy diffusion weighted MRI (DW-MRI) between 2016 and 2018 were included. Response to NAC was determined using tumor size changes, RECIST criteria and DW-MRI (changes in apparent diffusion coefficient (ADC)). Pathologic response on final histology was used as reference. Results 25 (69%) patients demonstrated pathologic response to NAC. Reduction in size was noted in 31 patients. ADC values increased on restaging MRI in 15 cases. Reduction in size alone predicted pathologic response with 92% sensitivity and 27% specificity compared to increased ADCs, 48% sensitivity and 73% specificity. Discussion Reduction in tumor size alone correlated with pathologic response to NAC. DW sequences alone had poor sensitivity but better specificity of predicting response. Caution is urged in using ADC values from DW-MRI to determine responses after NAC. Traditional size criteria should continue to be used for predicting pathologic response after NAC.