Objective To systematically assess imaging biomarkers on CT-based multimodal imaging for their being predictive versus prognostic biomarkers for intravenous and endovascular (IA) revascularization therapy, and for their prevalence. Methods Our retrospective study included patients suspected of acute ischemic stroke with admission work-up including a non-contrast head CT, perfusion CT, and CT angiography. Modified Rankin scores at 90 days were used as outcomes. For each imaging biomarker, the effect size of the test of interaction between the presence of the biomarker and the treatment effect was calculated, allowing the inference of a total sample size. The total sample size required was combined with the prevalence of the biomarker to determine the number needed to screen. Results In the 0-4.5-h time window, the two predictive biomarkers associated with the smallest number needed to screen were perfusion CT penumbra ≥ 20% (404 NNS) and CT angiography collateral score ≥ 2 (581 NNS). In the 3-9-h time window, the four predictive biomarkers associated with the smallest number needed to screen were clot burden score (CBS) on CT angiography (1181 NNS), clot length ≥ 10 mm (1924 NNS), CBS and clot length ≥ 10 mm (1132 NNS), and CBS and perfusion CT penumbra ≥ 100% (1374 NNS). Perfusion CT ischemic core was a prognostic biomarker in both time windows. Interpretation Predictive biomarkers need to be differentiated from prognostic biomarkers when being considered to select patients for a trial, and their prevalence should be assessed to determine the number needed to screen and overall feasibility of the trials.