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Purpose: To prospectively evaluate the prognostic impact of multimodal computed tomography-based imaging in ischemic stroke patients potentially eligible for reperfusion therapy. Methods: Anterior circulation stroke patients underwent non-contrast CT (NCCT), CT-angiography, and CT-perfusion within 12 h from symptom-onset. Patients could be treated with intravenous-tissue plasminogen activator (IV-tPA), endovascular or combined reperfusion therapies. Cerebral imaging profiles (IP) were NCCT-Alberta Stroke Program Early CT Score (ASPECTS) > 7 (IP1); NCCT-ASPECTS > 5 and proximal occlusion on CT-angiography (IP2); CT-perfusion mismatch between cerebral blood volume (CBV)-ASPECTS, and cerebral blood flow (CBF)-ASPECTS ≥ 2 (IP3). Favorable outcome was defined as modified Rankin Scale ≤ 2 at 3 months. Results: Of 102 included patients, 62 (61 %) received any reperfusion therapy. In IP2 and IP3, favorable outcome was more frequent in patients with reperfusion therapy than in those without; however, this did not reach statistical significance (IP2: 39 % vs 15 %, p = 0.26; IP3: 50 % vs 17 %; p = 0.31). No difference was seen in IP1 (58 % vs 58 %, p = 1.0). In IP2, patients with IV-tPA alone achieved better functional outcome (50 % vs 11 %, p = 0.03) and lower mortality (0 % vs 28 %, p = 0.045) than those without. Conclusions: Our results suggest a benefit with imaging profile selection based upon the combination of a small-to-moderate-sized infarction and a visible intracranial occlusion in patients receiving IV-tPA. Reperfusion therapy may be futile in patients without proven vessel occlusion. [ABSTRACT FROM AUTHOR]