Background: When penumbral imaging shows “total mismatch” (large perfusion lesion and no irreversibly infarcted core), the entirety of jeopardized brain is still salvageable and the benefits of reperfusion therapy may be enhanced. The frequency, characteristics, and reperfusion therapy outcomes of total mismatch patients has not been well-characterized. Methods: Analysis of consecutive acute cerebral ischemia patients in anterior circulation undergoing CT or MR penumbral imaging prior to intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT). Patients were classified in four groups: 1) total mismatch (core 0% of perfusion lesion), 2) non-total but substantial mismatch (core 1-20% of perfusion lesion), 3) moderate or no mismatch (core 20-100% of perfusion lesion), and 4) small perfusion lesion (perfusion lesion volume <10 ml). Results: Among 180 patients, pretreatment imaging patterns were: total mismatch 28.9%, substantial mismatch 22.8%, moderate or no mismatch 22.8%, and small perfusion lesion 25.6%. Among total mismatch patients, the Tmax>6 sec perfusion lesion volume was 56.5 ml (IQR 28.3-85.6) and time from last known well to imaging was 89 mins (IQR 65-296). Compared to moderate patients, clinical features of total mismatch patients were: older (76.0 vs 65.9, p=0.006), lower NIHSS (median 12 vs 18, p=0.019), and more cardioembolism (76.9% vs 48.8%, p=0.005). Total mismatch patients more often had CT than MR (65.4% vs 14.6%, p=0.000), less ICA occlusion (15.4% vs 34.1%, p=0.035), and smaller perfusion lesions (median 56.5 vs 82.1 ml, p=0.007). Total mismatch patients were treated with combined IVT+EVT in 32.7%, IVT alone in 26.9%, and EVT alone in 40.4%. Freedom from disability (mRS 0-1) at discharge was more frequent, 35.6% vs 16.2%, p=0.049 and disability levels at day 90 were lower in total mismatch patients, mean mRS 2.7 vs 3.9, p=0.029. Conclusion: Total mismatch is present in one-quarter of patients undergoing reperfusion therapy, more often in older patients with cardioembolism as etiology of stroke. Total mismatch patients have better disability outcomes from reperfusion therapy, but more than half show disability indicating need for more complete reperfusion.