Background A low baseline Alberta Stroke Programme Early CT Score (ASPECTS) is strongly associated with low rates of favorable outcome in patients with acute stroke. Objective To evaluate the efficacy and safety of revascularization therapy in patient with ASPECTS =5 in anterior circulation infarct. Methods We retrospectively analyzed 108 consecutive patients presenting low ASPECTS on diffusion-weighted imaging. Sixty patients were treated by mechanical thrombectomy, including 34 patients who received simultaneously intravenous thrombolysis. A control group of 48 patients not eligible for reperfusion therapy gave us a perspective on the natural history. Clinical outcome was evaluated at 90 days using the modified Rankin Scale (mRS) score. Hemicraniectomy after malignant infarction, mortality, and symptomatic intracranial haemorrhage (sICH) were also reported. Results Thrombolysis in Cerebral Infarction 2b–3 was assessed in 75% of treated patients. Reperfusion therapy led to significantly reduced disability (mRS score 0–2) at 90 days compared with the control group (30% vs 2.1%, p<0.001), hemicraniectomy (3.3% vs 22.9%, p=0.002), and death at 90 days (25% vs 47.9%, p=0.01). The sICH level was similar in treated patients and in the control group (p=0.78). Patients aged =70 years in the thrombectomy group had a significantly better clinical outcome than older patients (37.5% vs 10%, p=0.02), regardless of baseline characteristics or recanalization rate. Conclusions In patients with acute stroke in the anterior circulation and ASPECTS =5 revascularization therapy contributes to a favorable clinical outcome at 90 days, especially in patients younger than 70 years.