Abstract Background Computed tomography perfusion (CTP) is frequently performed during the diagnostic workup of acute ischemic stroke patients. Yet, ischemic core estimates vary widely between different commercially available software packages. We assessed the volumetric and spatial agreement of the ischemic core on CTP with the follow-up infarct on diffusion-weighted imaging (DWI) using an automated software. Methods We included successfully reperfused patients who underwent endovascular treatment (EVT) with CTP and follow-up DWI between November 2017 and September 2020. CTP data were processed with a fully automated software using relative cerebral blood flow (rCBF) < 30% to estimate the ischemic core. The follow-up infarct was segmented on DWI imaging data, which were acquired at approximately 24 h. Ischemic core on CTP was compared with the follow-up infarct lesion on DWI using intraclass correlation coefficient (ICC) and Dice similarity coefficient (Dice). Results In 59 patients, the median estimated core volume on CTP was 16 (IQR 8–47) mL. The follow-up infarct volume on DWI was 11 (IQR 6–42) mL. ICC was 0.60 (95% CI 0.33–0.76), indicating moderate volumetric agreement. Median Dice was 0.20 (IQR 0.01–0.35). The median positive predictive value was 0.24 (IQR 0.05–0.57), and the median sensitivity was 0.3 (IQR 0.13–0.47). Severe core overestimation on computed tomography perfusion > 50 mL occurred in 4/59 (7%) of the cases. Conclusions In patients with successful reperfusion after EVT, CTP-estimated ischemic core showed moderate volumetric and spatial agreement with the follow-up infarct lesion on DWI, similar to the most used commercially available CTP software packages. Severe ischemic core overestimation was relatively uncommon.