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Background: There is uncertainty whether prior statin use (PSU) influences the outcomes of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Therefore, we conducted a systematic meta-analysis of published clinical trials to evaluate whether statin use combined with IVT therapy may be useful and safe. Methods: Electronic databases were searched for clinical trials that involved outcomes between PSU and nonstatin use (NSU) among stroke patients treated with IVT. Functional outcome measures were 3-month favorable outcome (modified Rankin scale [mRS] 0–2) and 3-month excellent outcome (mRS 0–1). Adverse outcome measures were 3-month all-cause mortality, intracranial hemorrhage (ICH) and symptomatic ICH (sICH). Data were extracted and used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) by Review Manager 5.4 software. Results: Eleven studies, totaling 13,745 patients (2,957 for PSU and 10,788 for NSU), met the inclusion criteria. Compared with NSU, PSU was associated with excellent outcome (OR=0.78; 95% CI, 0.70–0.88; p<0.0001), ICH (OR=1.26; 95% CI, 1.07–1.47; p=0.005) and sICH (ORNINDS=1.32; 95% CI, 1.06–1.64; p=0.01), whereas favorable outcome (OR=1.08; 95% CI, 0.86–1.35; p=0.50) and mortality (OR=1.11; 95% CI, 0.97–1.27; p=0.15) showed no significant difference between PSU and NSU. However, after combining the available multivariable data, associations with neither excellent outcomes (adjusted OR=0.92; 95% CI, 0.79–1.07; p=0.28) nor adverse outcomes (ICH: adjusted OR=1.11; 95% CI, 0.96–1.29; p=0.16; sICH: adjusted ORNINDS=1.21; 95% CI, 0.95–1.56; p=0.13) was found. Conclusions: PSU might neither positively nor negatively affect the outcomes of AIS patients treated by IVT. [ABSTRACT FROM AUTHOR]