With the incidence of cardiovascular disease (CVD) escalating annually, the significance of investigating the correlation between inflammatory markers and lipid-related indices, notably the neutrophil-to-lymphocyte ratio (NLR) and atherogenic index of plasma (AIP), is increasingly paramount. This study aimed to elucidate the distinct and combined roles of NLR and AIP concerning the incidence of CVD. Diagnoses of CVD were established based on self-reported standardized medical condition questionnaires from participants. NLR was computed by dividing the peripheral blood neutrophil count by the lymphocyte count. AIP was calculated as log [triglyceride (TG, mg/dL)/high-density lipoprotein cholesterol (HDL-C, mg/dL)]. The study's primary outcome was the incidence of CVD. To ensure the reliability and accuracy of the results, the analysis incorporated sample weights and complex survey designs. The final analysis included 13,184 individuals. Higher levels of NLR and AIP were independently associated with CVD. After adjusting for all variables, compared to Q1 of AIP or NLR, Q4 of AIP (OR 1.54, 95% CI: 1.19-1.98) and NLR (OR 1.54, 95% CI: 1.19-1.98) was significantly associated with CVD. The joint effects showed that participants with higher levels of NLR and AIP had a significantly higher OR of 1.41(1.06, 1.87). The combination of NLR and AIP has better predictive efficacy (AUC: 0.629) for CVD than alone. This cohort suggests combined effects between the NLR and AIP on CVD. Our findings provide clinical implications for monitoring and managing NLR and AIP levels to mitigate the development of CVD.