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•Severe aortic atheroma was an independent risk factor for 2-year MACCE following TAVR.•Severe aortic atheroma was associated with periprocedural ischemic stroke and CV death (≤30 d), and late stroke (>1 y post-TAVR).•Severe aortic atheroma constitutes a major harmful factor associated with periprocedural events and can affect late stroke post-TAVR. Although aorta atheroma morphology is associated with acute outcomes post-transcatheter aortic valve replacement (TAVR), its association with long-term outcomes post-TAVR remains unknown. This study evaluates the impact of severe aortic atheroma on long-term outcomes following TAVR. We enrolled 977 patients who underwent TAVR between February 2010 and May 2019, with available contrast-enhanced computed tomography data. Severe aortic atheroma was defined as protruding atheroma of ≥3mm thickness with protruding components, ulcerated atheroma with ulcer-like intimal disruption, and atheroma of ≥5mm thickness. The primary endpoint was 2-year major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of cardiovascular death, myocardial infarction, ischemic stroke, and heart failure, events classified as periprocedural (≤30 days), early (30 days to 1 year), and late (>1-year post-TAVR). Patients with severe aortic atheroma (n = 274, 28%) had a higher cumulative incidence of 2-year MACCE than those without (40.6% vs 28.9%, log-rank p = 0.0002), which was attributed to increased risks of ischemic stroke (13.8% vs 6.8%, log-rank p = 0.0012) and cardiovascular death (18.6% vs 10.8%, log-rank p = 0.0009). Severe aortic atheroma was an independent risk factors for 2-year MACCE (adjusted hazard ratio [aHR], 1.49, 95% CI 1.16 to 1.90). In the landmark analysis, severe aortic atheroma was independently associated with periprocedural ischemic stroke and cardiovascular death (aHR, 2.12, 95% CI 1.15 to 3.90 and aHR, 3.29, 95% CI 1.70 to 6.37, respectively), and late ischemic stroke (aHR, 3.71, 95% CI 1.35 to 10.2). Patients with severe aortic atheroma have an increased risk of 2-year MACCE post-TAVR.