Objective: The substantial clinical improvement in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT), combined with the poor response of proximal intracranial occlusions to intravenous thrombolysis (IVT), led to questions regarding the utility of bridging therapy (BT; IVT followed by MT) compared to direct mechanical thrombectomy (dMT) for AIS patients with large vessel occlusion (LVO). Methods: We aimed to investigate the comparative safety and efficacy of BT and dMT in AIS patients. We included all observational studies and post hoc analyses from randomized controlled clinical trials that provided data on the outcomes of AIS patients with LVO stratified by IVT treatment status prior to MT. Results: We identified 38 eligible observational studies (11,798 LVO patients, mean age = 68 years, 56% treated with BT). In unadjusted analyses, BT was associated with a higher likelihood of 3-month functional independence (odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.32-1.76), 3-month functional improvement (common OR [cOR] for 1-point decrease in modified Rankin Scale score = 1.52, 95% CI = 1.18-1.97), early neurological improvement (OR = 1.21, 95% CI = 1.83-1.76), successful recanalization (OR = 1.22, 95% CI = 1.02-1.46), and successful recanalization with ≤2 device passes (OR = 2.28, 95% CI = 1.43-3.64) compared to dMT. BT was also related to a lower likelihood of 3-month mortality (OR = 0.64, 95% CI = 0.57-0.73). In the adjusted analyses, BT was independently associated with a higher likelihood of 3-month functional independence (adjusted OR = 1.55, 95% CI = 1.26-1.91) and lower odds of 3-month mortality (adjusted OR = 0.80, 95% CI = 0.66-0.97) compared to dMT. The two groups did not differ in functional improvement (adjusted cOR = 1.24, 95% CI = 0.89-1.74) or symptomatic intracranial hemorrhage (adjusted OR = 0.87, 95% CI = 0.61-1.25).Interpretation: BT appears to be associated with improved functional independence without evidence for safety concerns, compared to dMT, for AIS patients with LVO.