Recent randomized control trials (RCTs) established that mechanical thrombectomy is superior to medical therapy for patients with stroke due to a large vessel occlusion. To compare the safety and efficacy profile of the different mechanical thrombectomy strategies. A random-effects meta-analysis was performed and the I2 statistic was used to assess heterogeneity according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Nineteen studies with a total of 2449 patients were included. No differences were identified between the stent retrieval and direct aspiration groups in terms of modified Thrombolysis in Cerebral Infarction (mTICI) 2b/3 and mTICI 3 recanalization rates, and favorable outcomes (modified Rankin Scale [mRS] ≤ 2). Adverse event rates, including 90-d mortality, symptomatic intracerebral hemorrhage (sICH), and subarachnoid hemorrhage (SAH), were similar between the stent retrieval and direct aspiration groups. The use of the stent retrieval was associated with a higher risk of vasospasm (odds ratio [OR]: 2.98; 95% confidence interval [CI]: 1.10-8.09; I2: 0%) compared to direct aspiration. When compared with the direct aspiration group, the subgroup of patients who underwent thrombectomy with the combined approach as a first-line strategy had a higher likelihood of successful mTICI 2b/3 (OR: 1.47; 95% CI: 1.02-2.12; I2: 0%) and mTICI 3 recanalization (OR: 3.65; 95% CI: 1.56-8.54), although with a higher risk of SAH (OR: 4.33; 95% CI: 1.15-16.32). Stent retrieval thrombectomy and direct aspiration did not show significant differences. Current available evidence is not sufficient to draw conclusions on the best surgical approach. The combined use of a stent retriever and aspiration as a first-line strategy was associated with higher mTICI 2b/3 and mTICI 3 recanalization rates, although with a higher risk of 24-h SAH, when compared with direct aspiration. Copyright © 2019 by the Congress of Neurological Surgeons.