Purpose <p>This study aimed to evaluate the necessity of whole-body computed tomography (CT) in patients with acute ischemic stroke (AIS) and to assess the usefulness of a simple imaging protocol combining brain CT perfusion (CTP) and whole-body CT using low-tube voltage and split-bolus injection (SPBI).</p> Methods <p>We retrospectively analyzed 123 patients with suspected AIS who underwent both brain CTP and whole-body CT between April 2022 and May 2025. Image quality, vascular and parenchymal CT values, diagnostic findings, and incidence of post-contrast acute kidney injury (PC-AKI) were assessed. A control group of 115 patients who underwent dynamic contrast-enhanced CT of the chest and abdomen was used for comparison.</p> Results <p>The proposed protocol achieved high CT values (≥ 350 HU) in major vessels and comparable CT enhancement in organs compared to the control group. Visual assessment yielded very high scores (vessels, 4.975; organs, 3.725) and complete inter-reader agreement (vessels, k = 0.98; organs, k = 0.877). Only one patient (0.8%) who underwent mechanical thrombectomy developed PC-AKI. Whole-body CT revealed clinically significant vascular disease (including aortic dissection, pulmonary embolism, and severe carotid stenosis) in 14.6% of cases and incidental suspected malignancy in 5.7% of cases.</p> Conclusion <p>Following brain CTP, whole-body CT enables the detection of significant vascular and incidental findings in patients with suspected AIS and provides valuable diagnostic information. This protocol, which utilizes low-tube voltage and SPBI, is a simple, time-efficient, and safe method that enhances vascular and organ contrast, supporting its clinical utility in AIS diagnosis.</p> Graphical abstract <p></p>