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The purpose of the present study was to determine how accurately relative cerebral blood flow (RCBF) and relative cerebrovascular reactivity (RCVR) to acetazolamide assessed using brain perfusion single-photon emission computed tomography (SPECT) detected misery perfusion identified on positron emission tomography (PET) in adult patients with ischemic moyamoya disease (MMD). Oxygen extraction fraction (OEF), RCBF, and RCVR were assessed using 15O gas PET and N-isopropyl-p-[123I]-iodoamphetamine SPECT without and with acetazolamide challenge, respectively, in 45 patients. Regions of interest (ROIs) were automatically placed in the five middle cerebral artery (MCA) territories in the symptomatic cerebral hemisphere and in the ipsilateral cerebellar hemisphere using a three-dimensional stereotaxic ROI template. For RCBF and RCVR to acetazolamide, the ratio of the MCA ROI to cerebellar ROI was calculated. Of the five MCA ROIs in the symptomatic cerebral hemisphere in each patient, the ROI with the highest and lowest OEF value (two ROIs per patient) was selected for analyses. A significant square or linear correlation was observed between the OEF and RCBF (correlation coefficient, 0.780) or RCVR (correlation coefficient, − 0.345), respectively. The area under the receiver operating characteristic curve for detecting misery perfusion (OEF > 51.3%) was significantly greater for the RCBF than for the RCVR (difference between areas, 0.221; p