Objective To evaluate the collateral circulation status with four-dimensional computed tomography angiography (4D-CTA) after acute ischemic stroke (AIS) and analyze its correlation with prognosis. Methods Baseline data and imaging data of 47 AIS patients who admitted in our hospital from January to September 2020 and finally included in this study were collected and analyzed. All of them received 4D-CTA within 4.5 h after onset. The level of cerebral collateral circulation was assessed by multi-phase CT angiography (mCTA) scores and regional leptomeningeal collateral (rLMC) scores. The 90-day modified Rankin score (mRS) was used to evaluate the neurological prognosis, and the patients were divided into poor collateral circulation group (n=19) and good collateral circulation group (n=28) according to mRS. SPSS statistics 25.0 was used to analyze the data, and Chi-square test, student′s t test or rank sum test was used for inter-comparison depending on data types. Spearman correlation analysis was employed for the correlations among indicators. Logistic regression analysis was performed to analyze the factors affecting poor neurological prognosis in AIS patients. Receiver operating characteristic (ROC) curve was drawn to assess the predictive values of these indicators. Results Compared with the good collateral circulation group, the poor collateral circulation group had significantly higher National Institutes of Health Stroke Scale (NIHSS) score, larger penumbra volume (Tmax>6 s) and infarct core volume (rCBF<30%), smaller mismatch ratio, lower mCTA score, rLMC score and 90-day mRS score (P<0.05). mCTA score was negatively correlated with baseline NIHSS score, penumbra volume (Tmax>6 s), infarct core volume (rCBF<30%), and mismatch ratio, and positively correlated with rLMC score and 90-day mRS score. rLMC score had negative correlations with baseline NIHSS score, penumbra volume (Tmax>6 s), infarct core volume (rCBF<30%), mismatch ratio, and 90-day mRS score, and positive correlation with mCTA score. The results of multivariate logistic regression analysis showed that mCTA score and baseline NIHSS score were both predictors of poor neurological prognosis in AIS patients. ROC curve indicated that combination of mCTA score+baseline NIHSS score showed better predictive values for poor neurological prognosis in AIS patients than a single index, with an area under the ROC curve (AUC) of 0.918, a sensitivity of 89.6%, and a specificity of 92.4%. Conclusion mCTA score+baseline NIHSS score has a better value for predicting the poor neurological prognosis in AIS patients. When the mCTA cerebral collateral circulation score less than 3 and the baseline NIHSS score greater than 5, it indicates that neurological prognosis is poor in the patients.