Abstract: Objective: To explore the associations between organochlorine pesticides (OCPs) and cardiovascular disease (CVD) in the general population. Methods: A cross-sectional study was adopted, and 6,009 residents who met the inclusion and exclusion criteria from the National Health and Nutrition Examination Survey (NHANES) (2005-2016) were enrolled. General data, physical examination, and laboratory test results were collected from the participants. Seven types of OCPs were analyzed, including β-hexachlorocyclohexane (β-HCH), hexachloro-benzene (HCB), oxychlordane (OXY), trans-nonachlor (T-NONA), 2,2-Bis (4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE), 2,2-Bis(4-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT) and Mirex. The participants were divided into a control group (n=5,499) and a CVD group (n=510) according to the pre-sence or absence of CVD. Multivariate logistic regression analysis and restricted cubic spline (RCS) models were used to analyze the associations between individual exposure to OCPs and CVD risk in the population. The associations between the joint exposure to OCPs and CVD risk were further analyzed using Bayesian kernel machine regression (BKMR) and quantile g-computation (Qgcomp) models. Results: Results from the multivariate logistic regression analysis showed that, after adjusting for confounders, elevated concentrations of β-HCH, OXY, T-NONA, p, p'-DDE and Mirex were associated with an increased risk of CVD (P＜0.05). Compared with the first quartile of concentration, the CVD risk associated with β-HCH, OXY, T-NONA, p,p'-DDE and Mirex at the fourth quartile concentration increased by 3.19-fold, 2.96-fold, 6.26-fold, 2.40-fold and 1.89-fold, respectively. The RCS model revealed nonlinear dose-response relationships between β-HCH, OXY, T-NONA, Mirex and CVD risk (P＜0.05). The results from the BKMR model indicated a positive joint effect of OCPs mixture on CVD risk, with OXY likely being one of the major contributors. When the concentrations of other OCPs were fixed at the 25th, 50th, and 75th percentiles, OXY was positively associated with CVD risk. Additionally, potential interactions were observed between OXY and β-HCH, OXY and p,p'-DDE, as well as OXY and Mirex. The Qgcomp model verified the stability and validity of the BKMR, with only p,p'-DDE exerting a negative effect. The positive weights were observed in the following order: OXY, T-NONA, Mirex, and β-HCH. Conclusion: Joint exposure to OCPs is associated with an increased risk of CVD. OXY is the major component driving the associations, suggesting that it may serve as an independent risk factor for increased CVD risk.