Background and ObjectivesTo determine whether carotid plaque inflammation identified by ¹⁸F-fluorodeoxyglucose (¹⁸FDG)-PET is associated with late (5-year) recurrent stroke.MethodsWe did an individual-participant data pooled analysis of 3 prospective studies with near-identical study methods. Eligible patients had recent nonsevere (modified Rankin Scale score ≤3) ischemic stroke/TIA and ipsilateral carotid stenosis (50%–99%). Participants underwent carotid ¹⁸FDG-PET/CT angiography ≤14 days after recruitment. ¹⁸FDG uptake was expressed as maximum standardized uptake value (SUV_max) in the axial single hottest slice of symptomatic plaque. We calculated the previously validated Symptomatic Carotid Atheroma Inflammation Lumen-Stenosis (SCAIL) score, which incorporates a measure of stenosis severity and ¹⁸FDG uptake. The primary outcome was 5-year recurrent ipsilateral ischemic stroke after PET imaging.ResultsOf 183 eligible patients, 181 patients completed follow-up (98.9%). The median duration of follow-up was 4.9 years (interquartile range 3.3–6.4 years, cumulative follow-up period 901.8 patient-years). After PET imaging, 17 patients had a recurrent ipsilateral ischemic strokes at 5 years (recurrence rate 9.4%, 95% confidence interval [CI] 5.6%–14.6%). Baseline plaque SUV_max independently predicted 5-year ipsilateral recurrent stroke after adjustment for age, sex, carotid revascularization, stenosis severity, NIH Stroke Scale score, and diabetes mellitus (adjusted hazard ratio [HR] 1.98, 95% CI 1.10–3.56, p = 0.02 per 1–g/mL increase in SUV_max). On multivariable Cox regression, SCAIL score predicted 5-year ipsilateral stroke (adjusted HR 2.73 per 1-point increase, 95% CI 1.52–4.90, p = 0.001).DiscussionPlaque inflammation–related ¹⁸FDG uptake improved identification of 5-year recurrent ipsilateral ischemic stroke. Addition of plaque inflammation to current selection strategies may target patients most likely to have late and early benefit from carotid revascularization.Classification of EvidenceThis study provides Class I evidence that in individuals with recent ischemic stroke/TIA and ipsilateral carotid stenosis, carotid plaque inflammation–related ¹⁸FDG uptake on PET/CT angiography was associated with 5-year recurrent ipsilateral stroke.