Background Minor stroke is common and may represent up to two-thirds of cases of acute ischemic stroke. The cost-effectiveness of CT angiography in patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤6) is not well established. Purpose To evaluate cost-effectiveness of CT angiography in the detection of large-vessel occlusion (LVO) in patients with acute minor stroke (NIHSS score ≤6). Materials and Methods A Markov decision-analytic model with a societal perspective was constructed. Three different management strategies were evaluated: (a) no vascular imaging and best medical management, (b) CT angiography for all patients and immediate thrombectomy for LVO after intravenous thrombolysis, and (c) CT angiography for all and best medical management (including intravenous thrombolysis, with rescue thrombectomy for patients with LVO and neurologic deterioration). One-way, two-way, and probabilistic sensitivity analyses were performed. Results Base-case calculation showed that CT angiography followed by immediate thrombectomy had the lowest cost ($346 007) and highest health benefits (9.26 quality-adjusted life-years [QALYs]). CT angiography followed by best medical management with possible rescue thrombectomy for patients with LVO had a slightly higher cost ($346 500) and lower health benefits (9.09 QALYs). No vascular imaging had the highest cost and lowest health benefits. The difference in health benefits compared with the CT angiography and immediate thrombectomy strategy was 0.39 QALY, which corresponds to 142 days in perfect health per patient. The conclusion was robust in a probabilistic sensitivity analysis. CT angiography was cost-effective when the probability of LVO was greater than 0.16% in patients with acute minor stroke. The net monetary benefit of performing CT angiography was higher in younger patients ($68 950 difference between CT angiography followed by immediate thrombectomy and no vascular imaging in 55-year-old patients compared with $20 931 in 85-year-old patients). Conclusion Screening for large-vessel occlusion with CT angiography in patients with acute minor stroke is cost-effective and associated with improved health outcomes. Undetected large-vessel occlusion in the absence of vascular imaging results in worse health outcomes and higher costs. © RSNA, 2020 Online supplemental material is available for this article.