The effect of changes in the acquisition parameters on Diffusion Tensor Imaging (DTI) has been studied, but for very specific situations. A whole-brain comparison of 54 episodic migraine (EM) and 56 chronic migraine (CM) patients, using diffusion schemes of 61, 40 and 21 gradient orientations, was performed. Statistical comparisons were repeated reducing the sample size until no significant differences were found. Higher number of regions with significant lower axial diffusivity in CM compared to EM were found using 61 gradient directions. With a larger sample size, results with 40 and 21 directions were equivalent to results acquired with 61 directions.