Background: Cerebrovascular complications (CVC) in infective endocarditis (IE) are common. The only established treatments to reduce the incidence of CVC in IE are antibiotics and in selected cases early cardiac surgery. Potential effects of previously established antiplatelet therapy are under debate. Methods: In a prospective cohort study in Sweden and Demark, the influence of previously established antiplatelet therapy on CVC incidence and mortality in IE was assessed using logistic regression models. Results: Among 684 left-sided definite IE episodes, 23.0% were seen in patients on established antiplatelet therapy (96% acetylsalicylic acid). Patients on antiplatelet therapy were older and significantly more often had a history of congestive heart failure prior to IE diagnosis. No difference in CVC rate was seen between patients with and without ongoing antiplatelet therapy (23.6% vs 25.0%, adjusted odds ratio (AOR) 0.8, 95% confidence interval (CI) 0.481.5). Ischemic stroke, which occurred in 115 episodes (16.8%), was the most common cerebral lesion, and haemorrhagic complications were seen in 16 (2.3%) patients without correlation to chronic antiplatelet therapy. Unadjusted 1-y mortality was higher for patients on previously established antiplatelet therapy (33.8% vs 24.1%, odds ratio (OR) 1.6, 95% CI 1.12.4), but after adjustment for covariables associated with mortality an opposite statistical trend was seen (AOR 0.7, 95% CI 0.41.1). Conclusions: The incidence of symptomatic CVC in IE patients was not reduced by previously established antiplatelet therapy. One-y mortality was higher in patients on antiplatelet therapy in univariate analysis, but after multivariable modelling this association was lost.