In the bolus tracking technique with computed tomography (CT) or magnetic resonance imaging, cerebral blood flow (CBF) is computed from deconvolution analysis, but its accuracy is unclear. To evaluate the reliability of CT perfusion (CTP)-derived CBF, we examined 27 patients with symptomatic or asymptomatic unilateral cerebrovascular steno-occlusive disease. Results from three deconvolution algorithms, standard singular value decomposition (sSVD), delay-corrected SVD (dSVD), and block-circulant SVD (cSVD), were compared with (15)O positron emission tomography (PET) as a reference standard. To investigate CBF errors associated with the deconvolution analysis, differences in lesion-to-normal CBF ratios between PET and CTP were correlated with prolongation of arterial-tissue delay (ATD) and mean transit time (MTT) in the lesion hemisphere. Computed tomography perfusion results strongly depended on the deconvolution algorithms used. Standard singular value decomposition showed ATD-dependent underestimation of CBF ratio, whereas cSVD showed overestimation of the CBF ratio when MTT was severely prolonged in the lesions. The computer simulations reproduced the trend observed in patients. Deconvolution by dSVD can provide lesion-to-normal CBF ratios less dependent on ATD and MTT, but requires accurate ATD maps in advance. A practical and accurate method for CTP is required to assess CBF in patients with MTT-prolonged regions.