Purpose To investigate whether patients with capsular stroke (CS) and patients with pontine stroke (PS) involving the motor pathway have different types of structural damage and reorganization. Materials and Methods With institutional review board approval and after obtaining written informed consent, structural magnetic resonance imaging data were prospectively acquired in 115 patients with CS, 47 patients with PS, and 116 control subjects by using four imagers from three hospitals. Patients with stroke lesions in the left and right hemispheres were analyzed (timing of follow-up imaging: mean, 597 days; range, 180-2070 days). The gray matter volume (GMV) of each voxel was compared among the three groups while controlling for the effects of age, sex, and imager. Multiple comparisons were corrected by using a false discovery rate method for voxel-wise comparisons and by using the Bonferroni method for post hoc comparisons. Results Both patients with CS and patients with PS exhibited a GMV reduction (6.18%-8.23%) in the ipsilesional anterior insular cortex and a GMV increase (5.11%-11.73%) in the supplementary motor area relative to control subjects (P < .0013). Moreover, a GMV reduction was observed in the ipsilesional sensorimotor cortex in all patients with CS (9.73%-10.41%) and in the cerebellum in all patients with PS (10.58%-15.81%). Additionally, a GMV increase was found in the precuneus in patients with PS with left lesions (17.23%) and in the middle frontal gyrus in patients with CS with right lesions (10.95%). Conclusion The different patterns of structural damage and reorganization in patients with CS versus those with PS may provide useful information in designing individualized rehabilitative strategies for these patients. © RSNA, 2017 Online supplemental material is available for this article.