Objective To investigate the clinical value of whole-brain CT perfusion combined with ankle-brachial index (ABI) in patients with acute cerebral ischemia. Methods A total of 105 patients who were suspected of having cerebral ischemia were selected in this study, including 33 patients in the abnormal ABI group and 72 patients in normal ABI group. Examination by a 320-detector row whole-brain computed tomography (CT) scan with CT angiography (CTA) and CT perfusion was given to all the patients with stable symptoms. The perfusion parameters, including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and delay time, were obtained. The brain perfusion images were evaluated by two experienced physicians, and then the positive predictive value, negative predictive value, sensitivity and specificity of ABI in predicting brain CT perfusion abnormalities were calculated. Results Sixty-eight patients showed brain CT perfusion abnormalities, manifested as prolonged MTT and TTP, increased, normal or reduced CBV, and normal or reduced CBF. The 68 patients included 25 with abnormal ABI and 43 with normal ABI. The rate of positive CT perfusion in the abnormal ABI group (75.8%,25/33) was significantly higher than that in the normal ABI group (59.7%,43/72; P=0.039); the relative MTT and the relative TTP in the abnormal ABI group were also significantly longer than those in the normal ABI group (P<0.05). The positive predictive value, negative predictive value, sensitivity, and specificity of ABI predicted brain CT perfusion abnormalities were 75.8%, 40.3%, 36.8%, and 78.4%, respectively. Conclusion Whole-brain CT perfusion can accurately evaluate the hemodynamic changes at an early stage; simple ABI examination has certain predictive value for brain perfusion abnormalities; and the combination of them may facilitate the earlier detection and treatment of cerebral ischemia.