Purpose <p>To analyze the number, location, and clinical significance of new ischemic lesions (NIL) after carotid stenting in patients with guided antiplatelet therapy. To evaluate factors leading to thromboembolic complications and silent ischemia. Secondarily, we compared the incidence of NIL among historical cohorts with guided and standard antiplatelet therapy.</p> Methods <p>We conducted a retrospective analysis of prospectively collected data from 171 patients who underwent carotid stenting in a single center between 2014 and 2023. Magnetic resonance imaging with diffusion-weighted images was performed before and after stenting. We evaluated NIL after the procedure and their dependence on patient demographics, degree of stenosis, instrumentation used, and antiplatelet therapy. The incidence of NIL was compared to three cohorts receiving more potent or guided antiplatelet therapy based on platelet function test (<i>n</i> = 689) and to seven cohorts receiving standard dual antiplatelet therapy with aspirin and clopidogrel (<i>n</i> = 2777), using the meta-analytical approach.</p> Results <p>New ischemic lesions were found in 15.8% of patients (27/171). We recorded five ischemic strokes (2.9%). Most NIL were located in the ipsilateral middle cerebral artery basin (91%), but they also occurred contralaterally or in another basin. Stenosis length ≥ 15&#xa0;mm (<i>p</i> = 0.012) was shown to be significantly associated with the development of NIL. The incidence of NIL in a center with guided antiplatelet therapy was distinctly lower compared to results of the studies with standard antiplatelet therapy, 15.8% vs. 28.3–51.3%.</p> Conclusion <p>Guided antiplatelet therapy in carotid stenting is safe and shows a lower incidence of new ischemic lesions on MR-DWI compared to results with standard antiplatelet therapy. In this study with guided antiplatelet therapy, NIL were only associated with greater stenosis length.</p>