Background and Purpose— Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed after stroke. We aimed to investigate whether potential antiplatelet or vasospastic effects have important clinical implications. Methods— Using data from Danish medical registries, we did a nationwide follow-up study among ischemic stroke patients between 2003 and 2009. We identified 5833 SSRI users, and propensity score matched these patients with nonusers in a 1:1 ratio, followed by Cox regression analysis to compute hazard ratios (HRs) of acute myocardial infarction, recurrent stroke, major bleeding, and death. Results— Median follow-up time (from 30 days after discharge to death/end of follow-up) was 1159 days. In total, 2.9% had myocardial infarction, 8.1% recurrent ischemic stroke, 20.2% major bleeding, 1.4% intracranial bleeding, and 34.4% died during follow-up. SSRI users had a lower risk of the combined outcome of myocardial infarction or recurrent ischemic stroke (adjusted HR, 0.77; confidence interval [CI], 0.62–0.96). However, the SSRI users also experienced a higher risk of overall major bleeding (adjusted HR, 1.33; CI, 1.14–1.55) and a nonsignificantly higher risk of intracranial bleedings (adjusted HR, 1.14; CI, 0.62–2.12). Mortality increased in SSRI users (adjusted HR, 1.13; CI, 1.00–1.28) and death caused by bleeding increased (adjusted HR, 1.89; CI, 0.97–3.66) as compared with death by other causes (adjusted HR, 1.11; CI; 0.98–1.26). Conclusions— SSRI use after ischemic stroke was associated with a lower risk of new cardiovascular events and also with an increased bleeding risk. There was an increased mortality among SSRI users, which may be related to the increased bleeding risk.