Background: and Purpose In-hospital onset stroke (IHOS) accounts for a significant proportion of large vessel occlusion acute ischemic strokes, leading to worse outcomes due to delays in evaluation and treatment. Limited data is available on the effectiveness of mechanical thrombectomy in IHOS patients. This study aims to assess the safety and efficacy of mechanical thrombectomy for patients with IHOS and compare the outcomes with those of community-onset strokes (COS). Methods: We conducted a systematic review and meta-analysis following established guidelines, by searching PubMed, Scopus, Web of Science, and Embase databases up to April 11, 2023. Eligible studies reporting outcomes of interest were included, and relevant data was extracted and analyzed using Stata software version 17.0. Results: In a meta-analysis of nine studies, comprising 540 cases of IHOS and 5,744 cases of COS, IHOS cases had a significantly lower rate of good functional outcomes on follow-up (35.46% vs. 40.74%, P<0.01) and a higher follow-up mortality rate (26.29% vs. 18.08%, P<0.01) compared to COS patients. Both groups had comparable successful recanalization rates (IHOS: 79.32% vs. COS: 81.44%, P=0.11), incidence rates of periprocedural complications (IHOS: 15.10%, COS: 12.96%, P=0.78), and symptomatic intracranial hemorrhage (IHOS: 6.24%, COS: 6.88%, P=0.67). It is worth noting that much of the observed effect size for mortality and good functional outcomes on follow-up was derived from only one and two studies, respectively. Conclusion While the current literature suggests that mechanical thrombectomy is a safe and effective treatment for IHOS, further research is necessary to comprehensively evaluate its impact, particularly during follow-up.