© 2018 American Academy of Neurology Objective We aimed to evaluate the association between cancer and cerebrovascular disease in a prospective cohort study with adjudicated cerebrovascular diagnoses. Methods We analyzed participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were 45 years and older and had Medicare coverage for 365 days before their baseline study visit. Participants with a history of cancer or cerebrovascular events were excluded. The time-dependent exposure was a new diagnosis of malignant cancer identified through Medicare claims algorithms. Participants were prospectively followed from their baseline study visit (2003-2007) through 2014 for the outcome of a neurologist-adjudicated cerebrovascular event defined as a composite of stroke (ischemic or hemorrhagic) or TIA. Cox regression was used to evaluate the association between a new cancer diagnosis and subsequent cerebrovascular events. Follow-up time was modeled in discrete time periods to fulfill the proportional hazard assumption. Results Among 6,602 REGARDS participants who met eligibility criteria, 1,149 were diagnosed with cancer during follow-up. Compared to no cancer, a new cancer diagnosis was associated with subsequent cerebrovascular events in the first 30 days after diagnosis (hazard ratio 6.1, 95% confidence interval 2.7-13.7). This association persisted after adjustment for demographics, region of residence, and vascular risk factors (hazard ratio 6.6, 95% confidence interval 2.7-16.0). There was no association between cancer diagnosis and incident cerebrovascular events beyond 30 days. Cancers considered high risk for venous thromboembolism demonstrated the strongest associations with cerebrovascular event risk. Conclusion A new diagnosis of cancer is associated with a substantially increased short-term risk of cerebrovascular events.