The mechanism for hypoattenuating leaflet thickening (HALT) after transcatheter aortic valve replacement is still not well elucidated, and the role of Lp(a) (lipoprotein[a]) and hs-CRP (high-sensitivity C-reactive protein) has rarely been studied. This study sought to test the hypothesis that the risk of HALT is associated with an elevated level of Lp(a) or hs-CRP. A total of 307 consecutive individuals who underwent a transcatheter aortic valve replacement procedure were included. All patients received their first postoperative computed tomography scans within 12 months, and raw data were analyzed on 3mensio software. HALT was defined as visually identified increased leaflet thickness with typical meniscal appearance and at least 2 different multiplanar reformation projections. Associations of Lp(a) or hs-CRP with the risk of HALT were evaluated using multivariable logistic regression analysis. The incidence of HALT within 12 months after transcatheter aortic valve replacement in this study was 36.2%, and the risk of HALT was associated with higher baseline Lp(a) (the multivariable adjusted odds ratio [OR] for every 10 mg/dL change was 1.18 [95% CI, 1.09-1.29]) and hs-CRP level (the multivariable adjusted OR for every 1 mg/L change was 1.08 [95% CI, 1.00-1.27]). Compared with individuals out of the top 25th percentile for both Lp(a) and hs-CRP, the multivariable adjusted OR for HALT was 4.74 (95% CI, 1.65-14.37) for the top 25th percentile. This result remained consistent after excluding patients receiving anticoagulant therapy. The top 25th percentile of Lp(a) level (≥40 mg/dL) combined with the top 25th percentile of hs-CRP level (≥3.5 mg/L) conferred a 4.74-fold risk of HALT.