Aim To explore the relationship between atherogenic index (AI) and serum anti-cardiolipin antibody (ACA) and anti-β2 glycoprotein 1 antibody (aβ2GP1), and to provide reference for the prevention and control of atherosclerosis (As). Methods 34 598 hospital patients were selected from the First Affiliated Hospital of Wenzhou Medical University from March 2017 to June 2018. Serum ACA, ACA-IgA, ACA-IgG, ACA-IgM, aβ2GP1, aβ2GP1-IgA, aβ2GP1-IgG, aβ2GP1-IgM, total cholesterol, high density lipoprotein cholesterol, homocysteine (Hcy) and apolipoprotein A1 (ApoA1) were detected. AI was calculated and the patients were divided into high-risk group (AI≥4) and low-risk group (AI＜4) according to AI. Correlation analysis was performed by statistical software. Results The positive rates of ACA and aβ2GP1 in high-risk group were higher than those in low-risk group (χ²＝23.276 and 17.603, all P＝0.000), and the levels of age, ACA-IgA, ACA-IgG, aβ2GP1-IgA, aβ2GP1-IgG and Hcy in high-risk group were also higher than those in low-risk group (all P＜0.05), while the level of ApoA1 was lower than that in low-risk group (P＝0.000). The correlation analysis showed that AI was positively correlated with ACA-IgA, ACA-IgG, aβ2GP1-IgA, aβ2GP1-IgG and Hcy (r＝0.8,0.2,0.4,0.4,0.142, all P＜0.01), and negatively correlated with ApoA1 (r＝－0.447, P＝0.000). Multivariate Logistic regression analysis showed that age, ACA-IgA, Hcy and aβ2GP1 were risk factors for As, and ApoA1 was protective factor for As. Conclusion With the increase of ACA-IgA, aβ2GP1, Hcy and age, the decrease of ApoA1, AI gradually increases, and As risk increases accordingly. Clinically, we should pay close attention to the elderly patients with abnormal ACA, aβ2GP1, Hcy and ApoA1 in order to prevent the occurrence of As.