Introduction: Several predictors have been described to early diagnose malignant middle cerebral artery infarction (MMI) and select patient for hemicraniectomy. Nevertheless, few studies have assessed them among patients with acute ischemic stroke undergoing mechanical endovascular thrombectomy (MET). The overall objective in this study was to evaluate these predictors in patients undergoing MET in the purpose to guide the medical care in the acute phase. Methods: We selected patients from a prospective local database which reference all patients eligible for treatment with Alteplase thrombolysis and/or mechanical endovascular thrombectomy in acute stroke. We investigated demographic, clinical, and radiological data. Multivariate regression analysis was used to identify clinical and imaging predictors of MMI. Results: In 32 months, 66 patients were included. Eighteen (27.3%) developed MMI. Malignant evolution was associated with: severity of neurological deficit and level of consciousness at admission, infarct size in DWI sequence and involvement of other vascular territories. Study groups didn't differ in terms of successful reperfusion. Two variables were identified as independent predictors of MMI: DWI infarct volume (p < 0.001) and time to thrombectomy (p = 0.018). A decision tree based on these two factors was able to predict malignant evolution with high specificity (100%) and sensibility (73%). Conclusion: Our study proposes a practical decision tree including DWI lesion volume and delay before thrombectomy to early and accurately predict MMI in a subgroup of patients with MCA infarction undergoing MET regardless to the status of reperfusion.