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The aim of this study was to investigate whether diffusion-weighted imaging (DWI) could be useful in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Sixty-seven surgically proven HCCs from 65 patients (54 men and 11 women with an age range of 35-75 years and a mean age of 56.0 years) were retrospectively analyzed. The signal intensities (SIs) of the lesions on preoperative diffusion-weighted (DW) images were visually categorized as isointense or hyperintense in comparison with the adjacent liver. We also quantitatively measured SIs and apparent diffusion coefficients (ADCs) by drawing regions of interest in HCCs and livers on DW images with b values of 50, 400, and 800 second/mm2 and on ADC map images. Logistic regression analyses were performed so that we could identify independent predictors of MVI among laboratory and DWI findings. A univariate analysis showed that a histological grade of 3, a larger tumor size, a higher SI ratio on DW images, and a lower ADC value were significantly associated with MVI. A multiple logistic regression analysis showed that a histological grade of 3 and the ADC value were independent predictors of MVI. With a cutoff of 1.11 × 10−3 mm2/second, the ADC value provided a sensitivity of 93.5% and a specificity of 72.2% for the prediction of MVI with an odds ratio of 24.5 (95% confidence interval = 4.14-144.8, P < 0.001). In conclusion, lower ADC values (1.11 × 10−3 mm2/second or less) can be a useful predictor of MVI during the preoperative evaluation of HCC. Liver Transpl 18:1171–1178, 2012. © 2012 AASLD.