Background. Cerebral hyperperfusion syndrome (CHS), a rare complication after cerebral revascularization, is a well-described phenomenon after carotid endarterectomy or carotid artery stenting. However, the imaging evidence of CHS after intravenous tissue plasminogen activator (iv tPA) for acute ischemic stroke (AIS) has not been reported. Case Report. Four patients were determined to have manifestations of CHS with clinical deterioration after treatment with iv tPA, including one patient who developed seizure, one patient who had a deviation of the eyes toward lesion with worsened mental status, and two patients who developed worsened hemiparesis. In all four patients, postthrombolysis head CT examinations were negative for hemorrhage; CT angiogram showed patent cervical and intracranial arterial vasculature; CT perfusion imaging revealed hyperperfusion with increased relative cerebral blood flow and relative cerebral blood volume and decreased mean transit time along with decreased time to peak in the clinically related artery territory. Vascular dilation was also noted in three of these four cases. Conclusions. CHS should be considered in patients with clinical deterioration after iv tPA and imaging negative for hemorrhage. Cerebral angiogram and perfusion studies can be useful in diagnosing CHS thereby helping with further management.