BACKGROUND: Evaluating health status changes following transfemoral carotid artery stenting (TF-CAS) is essential for assessing procedural success, but meaningful clinical changes are unknown. We aimed to determine minimal clinically important differences (MCIDs) and quantify health status improvement or worsening rates after TF-CAS using the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) registry data. METHODS: The SAPPHIRE registry included patients undergoing TF-CAS from 2010 to 2014 for both symptomatic and asymptomatic carotid stenosis. Baseline and 30-day health status were assessed using the SF-36 (2010-2012) for mental and physical component scores (MCS and PCS) and the EQ-5D (2012-2014) for 3 L Index and Visual Analog Scale (VAS) scores. For each score, we calculated the 30-day distribution-based MCID (0.5*standard deviations of baseline health status) by symptom status and the overall cohort (symptom-weighted MCIDs). The changes were then categorized as improved, deteriorated, or unchanged based on these MCIDs. RESULTS: Health status was assessed using the EQ-5D in 3930 patients and the SF-36 in 3018 patients (27.7% and 30.5% symptomatic, respectively). The MCIDs by symptom status were close, hence weighted MCIDs of 0.09 (Index), 11.00 (VAS), 4.70 (PCS), and 5.40 (MCS) were established. Across all subscales, 21.2%-26.1% of patients improved, 10.5%-16.7% worsened, and 57.2%-66.1% unchanged. CONCLUSIONS: We established thresholds for meaningful health status changes after TF-CAS using common generic instruments. At 30 days after TF-CAS, 70%-80% of patients no change or worsened, while 20%-30% improved. Carotid artery disease-specific instrument would provide better insights into of TF-CAS effects on health status.