A method to produce gradient encoding schemes that minimize the noise of diffusion tensor imaging (DTI) indices for selected fiber orientations has been developed. The accuracy of DTI measurements depends on the gradient encoding scheme used. Most current acquisition schemes contain diffusion directions uniformly distributed in 3D space in order to provide equal noise levels for fibers in any orientation. However, when considering specific fiber bundles such as the corticospinal tract (CST) or parts of fiber bundles, the range of fiber orientations of interest may be limited. We hypothesized that, when studying fiber tracts with a limited range of orientations, measuring diffusion in directions that are uniformly distributed in 3D space may be suboptimal for the noise levels of various DTI indices. Therefore, we first used simulations to determine six diffusion directions that minimize the noise of DTI measurements for selected fiber orientations. The resulting optimized set of directions was then tested on the right CST of a healthy human subject, and its performance was compared with that of conventional acquisition strategies. Both the simulations and the experiments on the human subject demonstrated that the new scheme significantly reduced the standard deviation of DTI indices for tensors with primary eigenvectors within a selected range of orientations.