AbstractPurpose:To compare apparent diffusion coefficients (ADCs) with distributed diffusion coefficients (DDCs) in high‐grade gliomas.Materials and Methods:Twenty patients with high‐grade gliomas prospectively underwent diffusion‐weighted MRI. Traditional ADC maps were created using b‐values of 0 and 1000 s/mm2. In addition, DDC maps were created by applying the stretched‐exponential model using b‐values of 0, 1000, 2000, and 4000 s/mm2. Whole‐tumor ADCs and DDCs (in 10−3 mm2/s) were measured and analyzed with a paired t‐test, Pearson's correlation coefficient, and the Bland‐Altman method.Results:Tumor ADCs (1.14 ± 0.26) were significantly lower (P = 0.0001) than DDCs (1.64 ± 0.71). Tumor ADCs and DDCs were strongly correlated (R = 0.9716; P < 0.0001), but mean bias ± limits of agreement between tumor ADCs and DDCs was −0.50 ± 0.90. There was a clear trend toward greater discordance between ADC and DDC at high ADC values.Conclusion:Under the assumption that the stretched‐exponential model provides a more accurate estimate of the average diffusion rate than the mono‐exponential model, our results suggest that for a little diffusion attenuation the mono‐exponential fit works rather well for quantifying diffusion in high‐grade gliomas, whereas it works less well for a greater degree of diffusion attenuation. J. Magn. Reson. Imaging 2010;31:531–537. © 2010 Wiley‐Liss, Inc.