OBJECTIVE: To elucidate the timeframe and spatial patterns of cortical reorganization after different stroke-induced basal ganglia lesions, we measured cortical thickness at five timepoints over a six-month period. We hypothesized that cortical reorganization would occur very early and that, along with motor recovery, it would vary based on the stroke lesion site. METHODS: Thirty-three patients with unilateral basal ganglia stroke and 23 healthy control participants underwent MRI scanning and behavioral testing. To further decrease heterogeneity, we split patients into two groups according to whether or not the lesions mainly affect the striatal motor network as defined by resting-state functional connectivity. A priori measures included cortical thickness and motor outcome, as assessed with the Fugl-Meyer scale. RESULTS: Within 14 days post-stroke, cortical thickness already increased in widespread brain areas (p=0.001), mostly in the frontal and temporal cortices rather than in the motor cortex. Critically, the two groups differed in the severity of motor symptoms (p=0.03) as well as in the cerebral reorganization they exhibited over a period of six months (Dice overlap index=0.16). Specifically, the frontal and temporal regions demonstrating cortical thickening showed minimal overlap between these two groups, indicating different patterns of reorganization. CONCLUSIONS: Our findings underline the importance of assessing patients early on and of considering individual differences, as patterns of cortical reorganization differ substantially depending on the precise location of damage and occur very soon after stroke. A better understanding of the macrostructural brain changes following stroke and their relationship with recovery may inform individualized treatment strategies. © 2020 American Academy of Neurology.