BACKGROUND: Predicting long-term clinical outcome based on the early acute ischemic stroke information is valuable for prognostication, resource management, clinical trials, and patient expectations. Current methods require subjective decisions about which imaging features to assess and may require time-consuming postprocessing. This studys goal was to predict ordinal 90-day modified Rankin Scale (mRS) score in acute ischemic stroke patients by fusing a Deep Learning model of diffusion-weighted imaging images and clinical information from the acute period. METHODS: A total of 640 acute ischemic stroke patients who underwent magnetic resonance imaging within 1 to 7 days poststroke and had 90-day mRS follow-up data were randomly divided into 70% (n=448) for model training, 15% (n=96) for validation, and 15% (n=96) for internal testing. Additionally, external testing on a cohort from Lausanne University Hospital (n=280) was performed to further evaluate model generalization. Accuracy for ordinal mRS, accuracy within ±1 mRS category, mean absolute prediction error, and determination of unfavorable outcome (mRS score >2) were evaluated for clinical only, imaging only, and 2 fused clinical-imaging models. RESULTS: The fused models demonstrated superior performance in predicting ordinal mRS score and unfavorable outcome in both internal and external test cohorts when compared with the clinical and imaging models. For the internal test cohort, the top fused model had the highest area under the curve of 0.92 for unfavorable outcome prediction and the lowest mean absolute error (0.96 [95% CI, 0.77-1.16]), with the highest proportion of mRS score predictions within ±1 category (79% [95% CI, 71%-88%]). On the external Lausanne University Hospital cohort, the best fused model had an area under the curve of 0.90 for unfavorable outcome prediction and outperformed other models with an mean absolute error of 0.90 (95% CI, 0.79-1.01), and the highest percentage of mRS score predictions within ±1 category (83% [95% CI, 78%-87%]). CONCLUSIONS: A Deep Learning-based imaging model fused with clinical variables can be used to predict 90-day stroke outcome with reduced subjectivity and user burden.