Abstract Purpose Randomized controlled trials (RCTs) demonstrated a treatment effect of endovascular thrombectomy in acute ischemic stroke with large infarct, commonly defined as an Alberta Stroke Program Early CT Score (ASPECTS) of 3–5. However, data on endovascular thrombectomy in patients with very low ASPECTS of 0–2 remain scarce. Methods We conducted a systematic review and meta-analysis of RCTs comparing endovascular thrombectomy versus medical treatment alone in acute ischemic anterior circulation stroke with very large infarct, defined as ASPECTS of 0–2. The primary outcome was the shift toward better functional outcomes on the 90-day modified Rankin Scale (mRS). Random effects meta-analysis was performed using the generic inverse variance method. Results Literature research identified four RCTs which evaluated the treatment effect of endovascular thrombectomy for large infarcts and provided a subgroup analysis of the mRS shift in patients with ASPECTS of 0–2. The pooled analysis showed a significant shift toward better 90-day mRS scores in favor of endovascular thrombectomy (pooled odds ratio, 1.62, 95% confidence interval, 1.29–2.04, P < 0.001). Conclusion This meta-analysis suggests a treatment effect of endovascular thrombectomy in specific patients with very low ASPECTS of 0–2, challenging the use of ASPECTS for treatment selection in acute ischemic stroke due to large vessel occlusion. An individual patient meta-analysis of RCTs would strengthen evidence in the treatment of patients with ASPECTS of 0–2. Graphic abstract