Background Corticospinal tract (CST) injury has been shown to exert a major influence on functional recovery after ischemic stroke. Purpose To evaluate the prognostic value of CST injury estimated using a recent developed tractometry-based method. Study Type Prospective. Population Forty-eight patients with CST damage induced by stroke lesion who underwent brain magnetic resonance imaging within 7 days from onset. Sequence Diffusion-weighted imaging (b = 1000 seconds/mm(2)) and diffusion kurtosis imaging (DKI) spin-echo echo-planar sequence with three b-values (0, 1250, and 2500 seconds/mm(2)) at 3.0 T. Assessment A recently developed approach that combines tract segmentation and orientation mapping was used for CST-specific tractography and tractometry. CST injury was estimated using the proposed method with diffusion metrics extracted from DKI sequence and with the first principal component (PC1) of the metrics. We also calculated the weighted lesion load (wLL) for comparison. Clinical evaluation included the National Institutes of Health Stroke Score in the acute phase and the modified Rankin scale at 3 months post-stroke. The correlations between CST injury and initial motor impairment, as well as the prognostic values of CST injury for functional outcomes were evaluated. Statistical Tests Pearson correlation and logistic regression. Area under the receiver operating characteristic curve. P < 0.05 was considered statistically significant. Results CST injury calculated with diffusion metrics except fractional anisotropy all showed significant correlations with initial motor impairment. PC1 achieved the largest correlation coefficient (R = 0.65) compared with wLL and other diffusion metrics. In addition to wLL, DKI_AK, AFD_total, and PC1 maximum all showed predictive values for functional outcomes. Data Conclusion Structural injury to CST is important for the assessment of the extent of injury and the prediction of functional outcome. The method proposed in our study could provide an imaging indicator to quantify the CST injury after ischemic stroke. Level of Evidence 2 Technical Efficacy Stage 1