We aimed to assess the association between Inflammatory Burden Index (IBI) and cardiovascular disease (CVD) in adult Americans.This cross-sectional investigation included people with comprehensive data on IBI and CVD from the National Health and Nutrition Examination Survey (NHANES) 2005-2010 database. C-reactive protein (CRP) × neutrophil/lymphocyte (NLR) count was used to calculate IBI. CVD included angina pectoris, stroke, congestive heart failure (CHF), and coronary heart disease (CHD). Subgroup analysis and weighted multivariate regression were utilized to analyze the independent association between CVD and IBI.A total of 15,325 adult Americans were involved. There were 9.57 % of subjects having CVD, which was increased with increasing IBI quartiles (Tertile 1: 4.64 %; Tertile 2: 7.71 %; Tertile 3: 10.63 %; Tertile 4: 15.29 %; p < 0.001). After full adjustment, multivariate logistic regression analysis demonstrated a positive correlation between IBI level and CVD prevalence (OR = 1.43; 95 % CI, 1.16-1.76, p < 0.001). Subgroup analyses and interaction tests showed that the association between IBI and the prevalence of CVD was not affected by sex, age, body mass index, race, hypertension, and diabetes mellitus.In adult Americans, There is an association between IBI levels and the prevalence of CVD. More large-scale future research is required to assess the effect of IBI on CVD.