Objectives <p>Atherosclerotic carotid artery disease (CarAD) is a significant contributor to the global burden of cerebrovascular diseases. Several positron emission tomography computed tomography (PET/CT) radiotracers showed promising results in identifying and assessing vulnerable carotid atherosclerotic plaque. This review aims to assess the current evidence surrounding the use and potential of multiple PET radiotracers in identifying vulnerable carotid atherosclerotic plaque.</p> Materials and methods <p>A scoping review of the literature was conducted for original peer-reviewed articles of PET studies published between 2010 and 2024 that used ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), ¹⁸F-sodium fluoride (¹⁸F-NaF), ¹⁸F-fluoromisonidazole (¹⁸F-FMISO), ⁶⁸Ga-DOTATATE, ⁶⁸Ga-Pentixafor, and ¹¹C-Acetate for the evaluation of vulnerable carotid atherosclerotic plaque. The Covidence platform facilitated the screening of articles and data extraction.</p> Results <p>37 studies matched the inclusion criteria. Seven (19%) included serial dual-tracer PET/CT with ¹⁸F-FDG/¹⁸F-NaF, ¹⁸F-FDG/¹⁸F-FMISO, ¹⁸F-FDG/⁶⁸Ga-DOTATATE, and ¹⁸F-FDG/⁶⁸Ga-Pentixafor. The remaining studies used PET/CT ¹⁸F-FDG (<i>N</i> = 26, 70%), ¹⁸F-NaF (<i>N</i> = 2, 5%), 11C-Acetate (<i>N</i> = 1, 3%) and ⁶⁸Ga-DOTATATE (<i>N</i> = 1, 3%). Substantial variation in PET/CT acquisition parameters such as uptake time (min) [¹⁸F-FDG: 50–180, ¹⁸F-NaF: 60–180, and ⁶⁸Ga-DOTATATE: 60–120], radiotracer dose (MBq) [¹⁸F-FDG: 185–555, ¹⁸F-NaF: 125–370] and analysis methods [target-to-background ratio and/or standardised uptake values] were observed with no clear consensus on what constitutes a standard approach for carotid plaque evaluation using PET/CT.</p> Conclusion <p>The use of multiple PET radiotracers may provide novel diagnostic insights into the diagnosis of CarAD and improve the identification of vulnerable carotid atherosclerotic plaque. However, protocol heterogeneity affects reproducibility, necessitating standardised imaging parameters and histological validation to enable future clinical use of PET for CarAD assessment.</p> Key Points <p><Emphasis Type="BoldItalic">Question</Emphasis> <i>Conventional atherosclerotic plaque assessments, focusing on vessel occlusion, lack predictive power for vulnerable carotid atherosclerotic plaque. Can multi-radiotracer PET/CT, targeting plaque metabolic processes, address this?</i></p> <p><Emphasis Type="BoldItalic">Findings</Emphasis> <i>Multi-radiotracer PET/CT demonstrates promising potential in detecting vulnerable carotid atherosclerotic plaque, but variability in data acquisition and analysis methods persists.</i></p> <p><Emphasis Type="BoldItalic">Clinical relevance</Emphasis> <i>This review shows that multi-radiotracer PET/CT may provide novel diagnostic insights for detecting vulnerable carotid atherosclerotic plaque, potentially enhancing risk assessment and identifying patients at higher risk of cerebrovascular events.</i></p>