Purpose: To demonstrate the application of repeatability coefficients to assess whether longitudinal changes in diffusion indices of white matter structures are true changes for individual patients undergoing radiation therapy (RT). Methods: Using test‐retest diffusion tensor datasets from National Biomedical Imaging Archive database, as a measure of uncertainty, the repeatability coefficients (RC) of diffusion indices within the segmented cingulum, corpus callosum, and fornix were estimated. Twenty‐two patients with low‐grade or benign tumor treated by partial brain radiation therapy participated in an IRB‐approved MRI protocol. The diffusion tensor images were acquired pre‐RT, 3 weeks during RT, at the end of RT, and 1, 6, and 18 months after RT. The upper and lower limits of 95% confidence interval (CI) of the estimated RC from the test and retest data were used to evaluate whether the longitudinal percentage changes in diffusion indices of the segmented structures in the individual patients were beyond the uncertainty and thus could be considered as true radiation‐induced changes. Results: Diffusion indices of the segmented white matter structures had different uncertainties. The estimated RCs ranged from 5.3% to 9.6% for fractional anisotropy (FA), from 2.2% to 6.8% for mean diffusivity (MD), from 2.4% to 5.5% for axial diffusivity (AD), and from 2.9% to 9.7% for radial diffusivity (RD). Overall, 23% of the patients had FA changes, 44% had MD changes, 50% had AD changes, and 50% had RD changes beyond the uncertainty ranges. In the fornix, 85.7% and 100% of the patients showed changes beyond the uncertainty range at 6 and 18 months after RT, respectively, demonstrating that radiation has a pronounced late effect on the fornix compared to other segmented structures. Conclusion: Assessments of repeatability and confidence interval of diffusion tensor measurements in white matter structures allow us to determine the true longitudinal change in individual patients. Supported in part by RO1 NS064973.