Aim To study the diagnostic and prognostic value of head and neck computed tomography angiography (CTA) combined with ambulatory arterial stiffness index in acute cerebral watershed infarction (ACWI). Methods 292 patients who met the diagnostic criteria of ischemic cerebrovascular disease in the Department of Neurology of Baoding Second Central Hospital from July 2018 to September 2020 were prospectively collected. All patients were examined by diffusion weighted imaging (DWI). According to the results of DWI, patients were divided into ACWI group (n＝134) and non-ACWI group (n＝158). All patients underwent head and neck CTA examination and neck ultrasound, to detect the presence, nature and location of carotid plaque and the stenosis, location and stenosis of head and neck vessels in patients. The prognosis of the patients was evaluated with the NIHSS. The general clinical data, NIHSS score at admission and discharge, ambulatory arterial stiffness index (AASI), vascular stenosis in the head and neck, location and stenosis were compared between the two groups. Multivariate analysis was conducted using Logistic regression model. Pearson test was used to analyze the correlation between AASI and head and neck CTA in patients with ACWI. ROC curve was used to evaluate the detection index of CTA in the head and neck and the effect of AASI on ACWI, and the factors affecting the prognosis of patients with ACWI were analyzed by establishing Cox proportional hazard regression model. Results Mean arterial pressure was the protective factor of ACWI on admission (P＜0.05). The degree of internal carotid artery (ICA) stenosis on the lesion side, the stenosis degree of MCA on the lesion side, the stenosis of multiple vessels on the lesion side and AASI were independent risk factors for ACWI (P＜0.05). ASSI was positively correlated with the degree of ICA stenosis, the degree of MCA stenosis and the number of stenotic vessels (P＜0.001). The diagnostic value of head and neck CTA combined with AASI in ACWI was greater than that in ACWI alone (P＜0.05). NIHSS score at discharge, focal side severe ICA stenosis, focal side MCA severe stenosis, lesion side multivessel stenosis and AASI were the key risk factors affecting the prognosis of ACWI patients (P＜0.05). Conclusion The degree of ICA stenosis on the lesion side, the stenosis degree of MCA on the lesion side, the stenosis of multiple vessels on the lesion side and AASI are independent risk factors for ACWI. Clinically, head and neck CTA combined with AASI can be used for early diagnosis and treatment of ACWI patients and improve the prognosis of the patients.