Background: Intravenous recombinant tissue plasminogen activator (rt-PA) is an approved treatment for acute ischemic stroke within 4.5 h of symptoms onset. Decompressive craniectomy (DC) has been shown as an effective therapeutic modality in malignant middle cerebral artery (MCA) infarction. As rt-PA could result in hemorrhagic complication during or after any surgery DC may be associated with severe bleeding after intravenous thrombolysis.Case Description: A 57-year-old woman was presented 90 min after the sudden onset of left hemiplegia. Despite intravenous thrombolytic therapy, she lost consciousness within 48 h and brain CT scan showed a right malignant MCA infarction associated with a small bleeding. DC was performed without any complication. The patient improved dramatically.Conclusion: DC could be done safety for malignant MCA infarction after unsuccessful intravenous thrombolytic therapy even the later was complicated with intra- infarction hemorrhage.