In preclinical studies, microplastics and nanoplastics have been found to be a potential risk factor for cardiovascular disease. However, there is a lack of clinical evidence that this risk extends to humans. The authors conducted a prospective, multicenter, observational study involving patients undergoing carotid endarterectomy. The excised carotid plaque specimens were analyzed for microplastics and nanoplastics. The primary endpoint of a composite of myocardial infarction, stroke, or death from any cause was compared among patients with evidence of microplastics and nanoplastics in plaque as compared against patients with a plaque that showed no evidence of microplastics and nanoplastics. A total of 304 patients were enrolled in the study, and 257 completed a mean follow up of 34 months. Polyethylene was detected in carotid artery plaque of 150 patients (58.4 percent), with a mean level of 21.7 μg per milligram of plaque. A total of 31 patients (12.1 percent) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2 μg per milligram of plaque. Patients in whom microplastics and nanoplastics were detected within the atheroma were at higher risk for a primary endpoint event than those in whom these substances were not detected (hazard ratio, 4.53; 95 percent confidence interval, 2.00 to 10.27; P<0.001).