Early detection of hemorrhagic transformation after reperfusion therapy is crucial in acute stroke treatment. Here, we evaluated the relationship between hemorrhagic transformation and post-reperfusion hyperperfusion using pulsed arterial spin labeling (ASL) perfusion MRI and (123)I-iodoamphetamine single-photon emission-computed tomography. Patients who developed hemorrhagic transformation showed significantly higher cerebral blood flow in the affected lesion after thrombolysis and/or endovascular intervention. Focal hyperperfusion (ipsilateral to contralateral ratio >1.5) was associated with hemorrhagic transformation after reperfusion (odds ratio, 9.3; 95% confidence interval, 1.4-64.0). Our findings suggest that post-reperfusion hyperperfusion on ASL could represent a reliable marker of hemorrhagic transformation.