OBJECTIVE: The association of lipoprotein(a) [Lp(a)] with atherosclerotic cardiovascular disease (ASCVD) risk can be modified by chronic systemic inflammation. The neutrophil-to-lymphocyte ratio (NLR) is a reliable and easily available marker of immune response to various infectious and non-infectious stimuli. The purpose of this study was to assess the combined effects of Lp(a) and NLR in predicting the ASCVD risk and coronary artery plaque traits. METHODS: This study included 1618 patients who had coronary computed tomography angiography (CTA) with risk assessment of ASCVD. CTA was used to evaluate the traits of coronary atherosclerotic plaques, and the association of ASCVD with Lp(a) and NLR was assessed by multivariate logistic regression models. RESULTS: Plasma Lp(a) and NLR were significantly increased in patients having plaques. High Lp(a) was defined as the plasma Lp(a) level > 75 nmol/L and high NLR as NLR > 1.686. The patients were grouped into four categories according to normal or high NLR and plasma Lp(a) as nLp(a)/NLR-, hLp(a)/NLR-, nLp(a)/NLR+ and hLp(a)/NLR+. The patients in the latter three groups had higher risk of ASCVD compared to the reference group nLp(a)/NLR-, with the highest ASCVD risk in the hLp(a)/NLR+ group (OR = 2.39, 95% CI = 1.49-3.83, = 0.000). The occurrence of unstable plaques was 29.94% in the hLp(a)/NLR+ group, which was significantly higher than groups nLp(a)/NLR+, hLp(a)/NLR- and nLp(a)/NLR- with 20.83%, 26.54% and 22.58%, respectively, and there was a significantly increased risk of unstable plaque in the hLp(a)/NLR+ group compared to the nLp(a)/NLR- group (OR = 1.67, 95% CI = 1.04-2.68, = 0.035). The risk of stable plaque was not significantly increased in the hLp(a)/NLR+ group compared to the nLp(a)/NLR- group (OR = 1.73, 95% CI = 0.96-3.10, = 0.066). CONCLUSION: The concomitant presence of elevated Lp(a) and higher NLR is associated with increased unstable coronary artery plaques in patients with ASCVD.