Background: Endovascular treatment (EVT) for acute ischemic stroke (AIS) patients presenting with Alberta Stroke Program Early CT Score (ASPECTS) 0–5 has not yet proven safe and effective by clinical trials. Objectives: The aim of the study was to assess whether EVT in AIS patients presenting with low ASPECTS is beneficial. Design: Systematic review and meta-analysis of available studies in accordance with the PRISMA statement. Data sources and Methods: We have searched MEDLINE, the Cochrane Central Register of Controlled Trials, and reference lists of articles published until 28 May 2022 with the aim to calculate (1) modified Rankin scale (mRS) score 0–3 at 3 months, (2) mRS score 0–2 at 3 months, (3) symptomatic intracranial hemorrhage (sICH), and (3) mortality at 3 months. Results: Overall, 24 eligible studies were included in the meta-analysis, comprising a total of 2539 AIS patients with ASPECTS 0–5 treated with EVT. The pooled proportion of EVT-treated patients achieving mRS 0–3 at 3 months was calculated at 38.4%. The pooled proportion of EVT-treated patients achieving mRS 0–2 at 3 months was 25.7%. Regarding safety outcomes, sICH occurred in 12.8% of patients. The 3-month pooled mortality was 30%. In pairwise meta-analysis, patients treated with EVT had a higher likelihood of achieving mRS 0–3 at 3 months compared with patients treated with best medical therapy (BMT, OR: 2.41). sICH occurred more frequently in EVT-treated patients compared with the BMT-treated patients (OR: 2.30). Mortality at 3 months was not different between the two treatment groups (OR: 0.71). Conclusion: EVT may be beneficial for AIS patients with low baseline ASPECTS despite an increased risk for sICH. Further data from randomized-controlled clinical trials are needed to elucidate the role of EVT in this subgroup of AIS patients. Registration: The protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO; Registration Number: CRD42022334417.