Patients with dementia due to Alzheimer's disease (AD) have increased risk of developing delirium. This study investigated the relationship between a magnetic resonance imaging (MRI)–derived biomarker associated with preclinical AD and postoperative delirium. Participants were older adults (≥70 years) without dementia who underwent preoperative MRI and elective surgery. Delirium incidence and severity were evaluated daily during hospitalization. Cortical thickness was averaged across a published set of a priori brain regions to derive a measure known as the “AD signature.” Logistic and linear regression was used, respectively, to test whether the AD signature was associated with delirium incidence in the entire sample (N = 145) or with the severity of delirium among those who developed delirium (N = 32). Thinner cortex in the AD signature did not predict incidence of delirium (odds ratio = 1.15, p = 0.38) but was associated with greater delirium severity among those who developed delirium (b = −1.2, p = 0.014). These results suggest that thinner cortices, perhaps reflecting underlying neurodegeneration due to preclinical AD, may serve as a vulnerability factor that increases severity once delirium occurs.