Background: Diffusion-tensor fractional anisotropy (FA) is an index of neural-fiber damage in patients following stroke. To better characterize FA, tract-based spatial statistics (TBSS) is frequently used, which involves spatial transformation into the standard brain space. Despite its utility, this technique is susceptible to space-occupying hematoma in patients with intracerebral hemorrhage. To correct this, “lesion making” has been proposed. Here, FA values from TBSS without lesion masking and TBSS with lesion masking were compared, and the clinical utility was evaluated. Methods: Forty patients from our previously published work were entered into the study. Diffusion-tensor imagings were acquired 14-21 days after onset and FA maps were generated. Lesion masks were produced in reference with nondiffusion (b = 0) brain images. Two types (with or without lesion masking) of TBSS were then performed. For both types, using individual data we extracted mean FA values within for the corticospinal tract (CST) and the superior longitudinal fasciculus (SLF). FA ratio (rFA) between the lesioned hemisphere and the unaffected hemisphere was then calculated. The two sets of the data were then compared by assessing residuals of mean root sum square error (RMSE). Results: Although rFA obtained from TBSS with lesion masking tended to be slightly smaller, the estimated RMSE was .025 for both the CST and the SLF. Conclusions: The estimated FA differences between the two sets of TBSS were very small. Considering the time for manual labor for producing lesion masks, regular TBSS without lesion masking may be sufficient in terms of clinical utility.