ObjectiveThe investigation purpose was to examine the correlation between the aggregate index of systemic inflammation (AISI) and rheumatoid arthritis (RA) by utilizing the NHANES database from the years 1999 to 2018.MethodsThe NHANES database was utilized to extract data spanning from 1999 to 2018. AISI, comprising neutrophils (NEU), monocytes (MONO), platelets (PLT), and lymphocytes (LYM), was computed based on counts. The identification of RA patients was accomplished through questionnaire data. To investigate the connection between AISI and RA, a weighted multivariate regression and subgroup analysis were conducted. In addition, restricted cubic splines (RCS) were employed for examining non-linear associations.ResultsThe study encompassed a total of 41,986 patients, among whom 2,642 (6.29%) were diagnosed with RA. Upon controlling for all covariates, the outcomes of the multivariate logistic regression assay demonstrated a statistically significant association between higher Ln(AISI) levels and elevated odds of RA (odds ratio [OR]: 1.097; 95% confidence interval [CI]: 1.096–1.099, p