Background: Recent studies have suggested that favorable venous outflow (VO) may be a promising imaging biomarker to predict clinical outcomes following reperfusion therapy in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). Methods: A comprehensive literature search was conducted in PubMed, Scopus, WOS, and Cochrane to identify studies that evaluated VO profiles, assessed using the Cortical Vein Opacification Score (COVES). The risk ratio (RR) and 95% confidence interval (CI) for the outcomes, including functional independence, assessed by modified rankin scale at 90 days (mRS 0–2), hemorrhagic infarction, parenchymal hematoma, 90-day mortality, intracranial hemorrhage (ICH), and symptomatic ICH (sICH), were calculated and analyzed using the ‘meta’ package in R version 4.4.1. Results: A total of six studies encompassing 2249 patients were included. Patients with favorable VO had a higher likelihood of achieving functional independence at 90 days (RR = 2.15; 95% CI: 1.35, 3.42; p = 0.01) and a lower incidence of 90-day mortality (RR = 0.39; 95% CI: 0.30, 0.51; p < 0.01), parenchymal hematoma (RR = 0.36; 95% CI: 0.27, 0.47; p < 0.01). Furthermore, sICH was less frequent in patients with favorable VO (RR = 0.39; 95% CI: 0.17, 0.89; p = 0.03). However, hemorrhagic infarction and any ICH did not differ significantly between the two groups (p-values: 0.06 and 0.32, respectively). Conclusion: VO is a promising imaging biomarker for predicting outcomes in patients with AIS-LVO following reperfusion therapy. Prospective clinical trials are warranted to investigate the predictive value of VO, assessed on multiphasic computed tomography angiography (CTA), as a prognostic marker in this patient population.