Few studies are available on the risk of ischemic stroke after a diagnosis of primary Sjögren's syndrome (PSS). This study investigated whether PSS increased the risk of ischemic stroke in a large, nationwide cohort. Data for 4,276 patients who were newly diagnosed with PSS from 2000 to 2006 and who did not have a stroke prior to diagnosis of PSS were obtained from the Registry of Catastrophic Illness in Taiwan. For each PSS patient, data for ten controls (matched by age, gender, comorbidities, and enrollment date) without systemic autoimmune disease or previous stroke were obtained from the Longitudinal Health Insurance 2000 database. All study subjects were followed up from the date of enrollment until they developed ischemic stroke, died, or until the end of 2006, whichever was earliest. To investigate if PSS was an independent factor in determining the risk of developing ischemic stroke, a Cox regression model was used with adjustment for age, gender, and comorbid disorders. Among 4,276 PSS patients and 42,760 controls, 669 subjects (51 PSS patients and 618 controls) developed ischemic stroke during the mean 3.7-year follow-up period (interquartile range 2.2-5.2 years). Patients with PSS and controls had a similar incidence of ischemic stroke occurrence (3.17/1,000 vs. 3.90/1,000 person years). Multivariate analysis adjusted for baseline covariates indicated that PSS did not increase the risk of ischemic stroke (adjusted hazard ratio: 0.84, 95 % confidence interval: 0.63-1.12, P = 0.244). PSS is not associated with an increased risk of ischemic stroke subsequent to diagnosis.