To assess the clinical value of mechanical thrombectomy (MT) combined with intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) by comparing it with the MT alone. In this study, we conducted a comprehensive meta-analysis of both observational and randomized controlled studies (RCTs) to investigate various outcomes. Our search for relevant studies was conducted between January 2011 and June 2022 in four major databases: PubMed, Embase, WOS, and Cochrane Library. We collected data on several outcomes, including functional independence (FI; defined as modified Rankin Scale score of 0 to 2), excellent outcomes (mRS 0–1), successful recanalization (SR), symptomatic intracerebral hemorrhage (sICH), any intracerebral hemorrhage (aICH), and mortality at three months or discharge. The primary efficacy outcome and safety outcome were FI and sICH, respectively, whereas excellent outcomes and SR were considered secondary efficacy outcomes. Additionally, mortality and aICH were analyzed as secondary safety outcomes. We employed the Mantel–Haenszel fixed-effects model for RCTs whenI2< 50%, otherwise the random-effects model was utilized. For observational studies and subgroup analyses, we used the random-effects model to minimize potential bias. A total of 55 eligible studies (nine RCTs and 46 observational studies) were included. For RCTs, the MT + IVT group was superior in FI (OR: 1.27, 95% CI: 1.11–1.46), excellent outcomes (OR: 1.21, 95% CI: 1.03–1.43), SR (OR: 1.23, 95% CI: 1.05–1.45), mortality (OR: 0.72, 95% CI: 0.54–0.97) in crude analyses. In adjusted analyses, the MT + IVT group reduced the risk of mortality (OR: 0.65, 95% CI: 0.49–0.88). However, the difference in FI between the MT + IVT group and the MT alone group was not significant (OR: 1.17, 95% CI: 0.99–1.38, Fig. 3a). For observational studies, the results of FI (OR: 1.34, 95% CI: 1.16–1.33), excellent outcomes (OR: 1.30, 95% CI: 1.09–1.54), SR (OR: 1.23, 95% CI: 1.05–1.44), mortality (OR: 0.70, 95% CI: 0.64–0.77) in the MT + IVT group were better. Additionally, the MT + IVT group increased the risk of hemorrhagic transformation (HT) including sICH (OR: 1.16, 95% CI: 1.11–1.21) and aICH (OR: 1.24, 95% CI: 1.05–1.46) in crude analyses. In adjusted analyses, significant better outcomes were seen in the MT + IVT group on FI (OR: 1.36, 95% CI: 1.21–1.52), excellent outcomes (OR: 1.49, 95% CI: 1.26–1.75), and mortality (OR: 0.73, 95% CI: 0.56–0.94). The MT + IVT therapy did improve the prognosis for AIS patients and did not increase the risk of HT compared with MT alone therapy.