BACKGROUND: Apolipoprotein B (ApoB) is widely recognized as a biomarker significantly associated with cardiovascular risk. However, the correlation between ApoB and the severity of coronary artery anatomical stenosis (Gensini score) in individuals aged 45 and above has not been fully studied. METHODS: A cross-sectional retrospective analysis was conducted, involving 818 patients who underwent coronary angiography. Fasting blood samples were collected to measure lipid parameters, including ApoB. The severity of coronary artery stenosis was assessed using the Gensini score, and patients were divided into two groups based on the median cut-off (<36 vs. ≥ 36). A multivariate regression model was used to evaluate the association between ApoB and the severity of stenosis after adjusting for potential confounding factors. RESULTS: Compared to the mild stenosis group (Gensini score < 36), the moderate-to-severe stenosis group (score ≥ 36) had significantly higher levels of ApoB (1.0 ± 0.3 vs. 0.9 ± 0.3 g/L) and LDL-c (p < 0.05), while HDL-c and ApoA levels were lower (p < 0.001). Multivariate regression analysis indicated that ApoB was independently associated with moderate-to-severe coronary stenosis (β = 46.1, 95% CI: 31.3-61.0 p < 0.001). Sensitivity analysis using continuous Gensini score confirmed the association (β = 22.57, 95% CI: 13.67-31.47, p < 0.0001). Dose-response analysis revealed that higher ApoB tertiles were associated with progressively higher Gensini scores (P for trend = 0.001). Stratified analysis revealed a consistent positive correlation between ApoB and Gensini scores across all clinical subgroups (all p < 0.05), with no significant interactions detected (all P for interaction > 0.05). CONCLUSION: ApoB levels are significantly positively correlated with the severity of coronary artery stenosis in the population aged ≥ 45 years, indicating its potential clinical application value in evaluation.