Routine head computed tomography (CT) is performed 24 h post-acute stroke thrombolysis and thrombectomy, even in patients with stable or improving clinical deficits. Predicting CT results that impact management could help prioritize patients at risk and potentially reduce unnecessary imaging. In this institutional review board (IRB)-approved retrospective study, data from 1461 consecutive acute ischemic stroke patients at our Comprehensive Stroke Center (n = 8943, 2012-2022) who received intravenous thrombolysis or endovascular therapy, exhibited stable or improving 24-h exams, and underwent 24-h follow-up head CT per standard acute stroke care guidelines. CT reports 24 h post-stroke were reviewed for edema, mass effect, herniation, and hemorrhage. The primary outcome was any clinically relevant 24-h CT finding that led to changes in antithrombotic treatment or blood pressure goals, extended intensive care unit (ICU) stays or hospitalizations, neurosurgical interventions, or administration of mannitol or hypertonic saline. Multivariable logistic regression identified independent predictors of clinically meaningful CT abnormalities. A 24-h CT score was developed and cross-validated. The mean age was 70 years, with 47% women. The median National Institutes of Health Stroke Scale (NIHSS) score at admission was 12 (interquartile range (IQR): 6-18). Stroke-related abnormalities on 24-h CT were present in 325 patients (22.2%), with 183 (12.5%) showing clinically relevant findings. Age, admission NIHSS, and blood glucose levels were independent predictors of clinically relevant 24-h CT findings. The final model C statistic was 0.72 (95% confidence interval (CI): 0.68-0.76) in the derivation cohort and 0.72 (95% CI: 0.67-0.75) in bootstrapping validation. The 24-h CT score was developed using these predictors: NIHSS score 5-15 (+3); NIHSS score ⩾16 (+5); age < 75 years (+1); admission glucose ⩾ 140 mg/dL (+1). The prevalence of clinically relevant CT findings was 4.3% in the low-risk group (24-h CT score ⩽ 4), 11.3% in the medium-risk group (score 5), and 21.4% in the high-risk group (score ⩾ 6). The 24-h CT score demonstrated good calibration. In patients undergoing thrombolysis or thrombectomy who undergo routine 24-h head CT despite remaining clinically stable or improving, only one in eight prove to have 24-h head CT findings that impact management. The 24-h CT score provides risk stratification that may improve resource utilization. A.S. and B.Z. have full access to the data used in the analysis in this article. Deidentified data will be shared after ethics approval if requested by other investigators for purposes of replicating the results.