Conflicting data exist on the safety and efficacy of IV thrombolysis (IVT) in patients with acute ischemic stroke (AIS) receiving dual antiplatelet pretreatment (DAPP). The aim of the present systematic review and meta-analysis is to assess the safety and outcome of DAPP history among patients with AIS treated with IVT. We performed a comprehensive literature review to identify studies that investigated the safety and efficacy of DAPP among patients with AIS treated with IVT. We identified 9 studies comprising 66,675 patients. In unadjusted analyses, DAPP was associated with a higher likelihood of pooled symptomatic intracranial hemorrhage (sICH; odds ratio OR 2.26; 95% confidence interval CI 1.39-3.67) and 3-month mortality (OR 1.47; 95% CI 1.25-1.73). DAPP was also related to higher odds of sICH according to Safe Implementation of Treatments in Stroke Monitoring Study (OR 2.71; 95% CI 2.05-3.59), European Cooperative Acute Stroke II (OR 2.23; 95% CI 1.46-3.40), and National Institute of Neurological Disorders and Stroke (OR 1.59, 95% CI 1.38-1.83) definitions. There was no association between DAPP and 3-month favorable functional outcome (FFO, modified Rankin Scale mRS score 0-1) and 3-month functional independence (FI; mRS score 0-2). In adjusted analyses, history of DAPP was not associated with pooled sICH (OR 2.03; 95% CI 0.75-5.52), 3-month mortality (OR 1.11; 95% CI 0.87-1.40), 3-month FFO (OR 0.92; 95% CI 0.77-1.09), and 3-month FI (OR 1.01; 95% CI 0.89-1.15). After adjustment for potential confounders, DAPP appears not to be associated with higher risk of adverse outcomes in patients with AIS treated with IVT.