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Objective: The randomized trials and pooled analysis showed improved outcome and reduced mortality in malignant middle cerebral artery [MMCA] undergoing decompressive hemicraniectomy (DHC) within 48 hours of stroke onset. This could be due to highly selective patient population in trials, not reflecting real world practice. Furthermore, with ischemic stroke being so common in the South Asian and Middle Eastern population, there still exists very little published data on DHC in MMCA stroke patients.Methods: Retrospective, multicenter cross-sectional study to measure outcome following DHC using the modified Rankin Scale [mRS] and dichotomized as favorable ≤4 or unfavorable >4, at three months.Results: In total 137 patients underwent DHC. At 90 days, mortality was 16.8%, 61.3% of patients survived with an mRS ≤4 and 38.7% had an mRS of >4. Age (55 years), diabetes [p=0.004], hypertension [p=0.021], pupillary abnormality [p=0.048], uncal herniation [p=0.007], temporal lobe involvement [p=0.016], additional infarction [MCA + ACA, PCA] [P=0.001], and infarction growth rates [P=0.025] was significantly higher in patients with unfavorable prognosis in univariate analysis. Multivariate analysis showed age, additional infarction, septum pellucidum deviation >1cm and uncal herniation to be associated with a significantly poor prognosis. Time to surgery had no impact on outcome [p=0.109].Conclusions: Similar to the effects observed in the studies from the West, DHC improves functional outcome in predominantly South Asian patients with MMCA stroke. Increasing age, MCA with additional infarctions, septum pellucidum deviation 1cm and uncal herniation were significant predictors of disability and poor functional outcomes. Time to surgery had no impact on functional outcome.