Background and Purpose-Brain imaging has continuously enhanced our understanding how different brain networks contribute to motor recovery after stroke. However, the present models are still incomplete and do not fit for every patient. The interaction between the degree of damage of the corticospinal tract (CST) and of corticocortical motor connections, that is, the influence of the microstructural state of one connection on the importance of another has been largely neglected. Methods-Applying diffusion-weighted imaging and probabilistic tractography, we investigated cross-network interactions between the integrity of ipsilesional CST and ipsilesional corticocortical motor pathways for variance in residual motor outcome in 53 patients with subacute stroke. Results-The main finding was a significant interaction between the CST and corticocortical connections between the primary motor and ventral premotor cortex in relation to residual motor output. More specifically, the data indicate that the microstructural state of the connection primary motor-ventral premotor cortex plays only a role in patients with significant damage to the CST. In patients with slightly affected CST, this connection did not explain a relevant amount of variance in motor outcome. Conclusions-The present data show that patients with stroke with different degree of CST disruption differ in their dependency on structural premotor-motor connections for residual motor output. This finding might have important implications for future research on recovery prediction models and on responses to treatment strategies.