Backgroundand Purpose: Current guidelines recommend the use of mechanical thrombectomy (MT) plus intravenous thrombolysis (aka bridging therapy, [BT]) for patients with anterior circulation large vessel occlusion (LVO) stroke. However, clinical equipoise exists in relation to the use of BT versus MT alone. Our objective is to compare the efficacy and safety of BT to MT for anterior circulation LVO.Methods:A systematic search of biomedical literature databases was performed from inception to October 29, 2021 to identify prospective and retrospective studies comparing the rates for functional independence (modified Rankin Scale score 0-2) and mortality at 90 days, symptomatic hemorrhage (sICH), and successful recanalization rates for MT and BT. Effect size was represented by odds ratio (OR) and analysis was done using random effects meta-analysis. Heterogeneity was assessed by I2 and Cochrane’s Q statistics.Results:Overall, 41 studies with 14885 patients were included. Mean age ± standard deviation (years) was 69±11 for BT and 70±11 for MT. All studies used alteplase as thrombolytic agent. BT group had 29% higher odds for functional independence (OR=1.29, 95% CI 1.16-1.44, I2=42%), 25% higher odds of successful reperfusion (OR=1.25, 95% CI=1.08-1.44, I2=42%) and a 31% decrease in odds for mortality (OR=.69, 95% CI .60-.80, I2=47%) compared with MT. sICH prevalence was similar between groups (OR=1.10, 95% CI=.95-1.28, I2=0%). Six of the studies were randomized clinical trials (RCT) with intention-to-treat analysis done in patients presenting directly to MT-capable centers. When analysis was restricted to these six RCT (n= 2333), no differences were observed in functional independence (OR=1.08, 95% CI=.91-1.27, I2=0%), sICH (OR=1.37, 95% CI=.95-1.97, I2=0%) or mortality (OR=.93, 95% CI=.74-1.16, I2=0%) between groups. However, successful reperfusion favored BT group (OR=1.35, 95% CI=1.06-1.73, I2=0%).Discussion:The odds for functional independence, successful reperfusion and mortality for the entire dataset favored the use of BT over MT (medium heterogeneity and low quality of the evidence). When analysis was restricted to RCT, both treatments had similar functional and safety outcomes (no heterogeneity), but recanalization rates favored BT group (no heterogeneity). Because these findings may differ in patients that present to non-MT-capable centers or with the use of other thrombolytic agents, further RCTs are needed.