It is important to predict the outcome of tissue plasminogen activator (tPA)-treated patients early after the treatment for considering the post-tPA treatment option. We assessed cerebral blood flow (CBF) of tPA-treated patients with single-photon emission computed tomography (SPECT) 1 hour after tPA infusion to predict the patient outcome. Technetium-99m-hexamethylpropyleneamine oxime SPECT was performed in 35 consecutive tPA-treated patients. Asymmetry index, a contralateral-to-ipsilateral ratio of CBF, was calculated to analyze CBF quantitatively. Hypoperfusion or hyperperfusion was defined as a decrease of 25% or more or a increase of 25% or more in asymmetry index, respectively. Of all 35 patients, 23 had only hypoperfusion, 8 had both hypoperfusion and hyperperfusion, 2 had only hyperperfusion, and 2 had no perfusion abnormality. When evaluating the association between hypoperfusion and outcome, hypoperfusion volumes were significantly correlated with the modified Rankin Scale at 3months (r=.634, P<.001). Hyperperfusion was observed in 10 patients (28.6%) and they showed a marked National Institutes of Health Stroke Scale score improvement in the first 24-hour period, which were significantly greater than those of 25 patients without hyperperfusion (P=.033). Eight patients (22.9%) with intracerebral hemorrhage (ICH) were all asymptomatic. Most ICHs were located in hypoperfusion areas, and no ICH was related to hyperperfusion. The results of the present study demonstrated that hypoperfusion volume was associated with poor outcome, whereas the presence of hyperperfusion seemed to be predictive of symptom improvement but not of development of ICH. Taken together, early post-treatment SPECT imaging seems to be a useful biomarker of outcome in tPA-treated patients.