Objective <p>To establish and validate a short-term prognostic model for acute ischemic stroke (AIS) patients undergoing intravenous thrombolysis based on multimodal CT.</p> Methods <p>A total of 180 patients with AIS were admitted to our hospital between January 2021 and December 2023, and divided into a modeling group and a validation group. Baseline characteristics were compared between cohorts. To identify determinants of short-term outcomes in AIS patients undergoing intravenous thrombolysis, both univariate and multivariate logistic regression models were employed for a comprehensive analysis. A predictive model for the short-term prognosis of these patients was constructed, and the application value of the model in predicting the short-term prognosis was evaluated with ROC analysis.</p> Results <p>The independent predictors of short-term prognosis in AIS patients treated with intravenous thrombolysis include NIHSS score, CBV, CBF, MTT, and TTP. Notably, the calibration curves for both training and validation cohorts closely resemble a straight line with a slope nearing unity, demonstrating excellent agreement between predicted and observed aspiration risks. The ROC analysis results showed that the model achieved an area under the curve (AUC) of 0.967. In the validation set, the area under the prediction curve of the model for the short-term prognosis was 0.828, with a standard error of 0.447 and the optimal cutoff value was 0.64.</p> Conclusion <p>By analyzing multimodal CT parameters, this study successfully established and validated a short-term prognostic model for AIS patients undergoing intravenous thrombolysis. The model demonstrated high predictive value.</p> Trial registration <p>Not applicable.</p>