<b><i>Introduction:</i></b> We sought to verify the predicting role of a favorable profile on computed tomography perfusion (CTP) in the outcome of patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) undergoing effective mechanical thrombectomy (MT). <b><i>Methods:</i></b> We retrospectively enrolled 25 patients with AIS due to LVO and with a CTP study showing the presence of ischemic penumbra who underwent effective MT, regardless of the time of onset. The controls were 25 AIS patients with overlapping demographics and clinical and computed tomography angiography features at admission who had undergone successful MT within 6 h from onset and without a previous CTP study. The outcome measure was the modified Rankin Scale (mRS) score at 90 days. <b><i>Results:</i></b> Sixty-four percent of the study patients had an mRS score of 0–1 at 90 days versus 12% of the control patients (<i>p</i> &#x3c; 0.001). Patients of the study group had a more favorable distribution of disability scores (median mRS [IQR] score of 0 [0–2] vs. 2 [2–3]). Multivariate analysis showed that the selection of patients based on a favorable CTP study was strongly associated (<i>p</i> &#x3c; 0.001) with a better neurological outcome. <b><i>Conclusions:</i></b> In our small-sized and retrospective study, the presence of ischemic penumbra was associated with a better clinical outcome in patients with AIS due to LVO after MT. In the future, a larger and controlled study with similar criteria of enrollment is needed to further validate the role of CTP in patient selection for MT, regardless of the time from the onset of symptoms.