Objective To evaluate the clinical usefulness of diffusion-weighted magnetic resonance imaging (DWI) in patients with pancreatic cancer by comparing the apparent diffusion coefficient (ADC) value with tumor differentiation. Methods 75 patients (39 Males, 26 Females; age range 36-76 years) with histologically confirmed pancreatic ductal adenocarcinoma (55 with moderately differentiated tumors and 20 with poorly differentiated tumors) and 49 healthy volunteers (29 Males, 20 Females; age range 21-62 years) underwent respiratory triggered DWI at 3.0 T before surgery. Apparent diffusion coefficient (ADC) values of normal pancreas head, body and tail as well as ADC values of the pancreatic adenocarcinomas were calculated and measured. The ADC values of normal pancreas and tumors were statistically analyzed and compared using Mann-Whitney U test. Comparison of two data sets of the tumor differentiation was also performed using Mann-Whitney U test. ROC curve was used to analyze the diagnostic power of ADC value. Results Mann-Whitney U tests showed ADC values differed significantly between pancreatic adenocarcinoma group [(1.36±0.14)×10-3mm2 /s] and normal pancreas head, body or tail groups[(1.66±0.34), (1.77±0.36), (1.62±0.38)×10-3mm2 / s, respectively] (all of the P=0.000). However, no association between ADC values of pancreatic adenocarcinoma and tumor differentiation was observed. With the global ADC values of normal pancreas as a reference, the area under the curve and the 95% confidence interval of ROC analysis were 0.863 and 79.5%-93.1%, respectively. The sensitivity and specificity were 75.5% and 85.3%, when ADC≤1.815×10-3mm2 /s was used as the cutoff value for the differential diagnosis of pancreatic adenocarcinoma from normal pancreas. Conclusion DWI had a better diagnostic accuracy in the diagnosis of pancreatic ductal adenocarcinoma. Although ADC values are significantly different between benign pancreas and pancreatic adenocarcinoma, no associations between ADC values and tumor differentiation were observed.