CONTEXT: Dysfunction of the thalamocortical pathway has been proposed as a putative underlying pathology of schizophrenia. Although the mechanisms involved remain unclear, postmortem studies suggest the involvement of altered neural projections from the thalamus to layers within the prefrontal cortex. OBJECTIVES: To investigate thalamocortical connectivity in schizophrenia and to examine its possible association with cortical thinning in vivo. DESIGN: Case-control cross-sectional study. SETTING: Department of Psychiatry at Kyoto University Hospital, Japan. PATIENTS AND OTHER PARTICIPANTS: A total of 37 patients with schizophrenia and 36 age-, sex-, and education-matched healthy controls recruited from the local community underwent diffusion-weighted imaging and T1-weighted 3-dimensional magnetic resonance imaging. MAIN OUTCOME MEASURES: Probabilistic tractography was performed to investigate thalamocortical pathways. Group differences in mean fractional anisotropy (FA) values were examined in the entire thalamocortical pathway, the thalamolateral prefrontal pathway, the thalamomedial prefrontal pathway, and the thalamo-orbitofrontal pathway. Surface-based analysis was performed to investigate cortical thickness, and the correlation between FA values and cortical thickness was examined. RESULTS: The patient group exhibited reduced FA values within the right thalamo-orbitofrontal pathway (P < .05 for the 8 group comparisons of FA, Bonferroni correction). In the patient group only, the mean FA value for this pathway was positively correlated with thickness of the right frontal polar and lateral orbitofrontal cortices (P < .05, clusterwise correction). CONCLUSIONS: These results suggest that, in schizophrenia, regional thalamocortical white matter pathology is specifically associated with cortical pathology in regions where fibers connect.