Objective: Conflicting data exist regarding the safety and efficacy of IV thrombolysis (IVT) in acute ischemic stroke (AIS) patients 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 AIS patients treated with IVT. Methods: We performed a comprehensive literature review to identify studies that investigated the safety and efficacy of DAPP among AIS patients treated with IVT. Results: We identified 9 studies comprising 66,675 patients. In unadjusted analyses, DAPP was associated with higher likelihood of pooled symptomatic intracranial hemorrhage (sICH, OR = 2.26, 95% CI 1.39–3.67) and 3-month mortality (OR = 1.47, 95% CI 1.27–1.73). DAPP was also related to higher odds of sICH according to SITS-MOST (OR = 2.71, 95% CI 2.05–3.59), ECASS II (OR=2.23, 95% CI 1.46–3.40) and NINDS (OR=1.59, 95% CI 1.38–1.83) definitions. There was no association between DAPP and 3-month favorable functional outcome (FFO, mRS 0-1), and 3-month functional independence (FI, mRS 0-2). In adjusted analyses, history of DAPP was not associated with pooled sICH (OR=2.03, 95% CI 0.75–5.25), 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). Conclusions: After adjustment for potential confounders DAPP appears not to be associated with higher risk of adverse outcomes in AIS patients treated with IVT.