In present study we aimed to validate the use of image-derived input functions (IDIF) in the kinetic modeling of cerebral blood flow (CBF) measured by [¹⁵O]H₂O PET by comparing with the accepted reference standard arterial input function (AIF). Additional comparisons were made to mean cohort AIF and CBF values acquired by methodologically independent phase-contrast mapping (PCM) MRI. Using hybrid PET/MRI an IDIF was generated by measuring the radiotracer concentration in the internal carotid arteries and correcting for partial volume effects using the intravascular volume measured from MRI-angiograms. Seven patients with carotid steno-occlusive disease and twelve healthy controls were examined at rest, after administration of acetazolamide, and, in the control group, during hyperventilation. Agreement between the techniques was examined by linear regression and Bland-Altman analysis. Global CBF values modeled using IDIF correlated with values from AIF across perfusion states in both patients (p<10⁻⁶, R²=0.82, 95% limits of agreement (LoA)=[-11.3–9.9] ml/100 g/min) and controls (p<10⁻⁶, R²=0.87, 95% LoA=[-17.1–13.7] ml/100 g/min). The reproducibility of gCBF using IDIF was identical to AIF (15.8%). Values from IDIF and AIF had equally good correlation to measurements by PCM MRI, R²=0.86 and R²=0.84, (p<10⁻⁶), respectively. Mean cohort AIF performed substantially worse than individual IDIFs (p<10⁻⁶, R²=0.63, LoA=[-12.8–25.3] ml/100 g/min). In the patient group, use of IDIF provided similar reactivity maps compared to AIF. In conclusion, global CBF values modeled using IDIF correlated with values modeled by AIF and similar perfusion deficits could be established in a patient group.