Objective: To examine the cross-sectional association between allostatic load and arthritis using data from the National Health and Nutrition Examination Survey (NHANES). Methods: Complete data on 7,714 adults were included in the analysis. An allostatic load (AL) index, comprising of multiple regulatory systems, was calculated from 11 biomarkers. Multivariate logistic regression was used to estimate the odds ratio (OR) for the association between allostatic load and arthritis, while accounting for confounders. Results: Significant positive associations were found between both continuous allostatic load (OR=1.12, 95% CI= 1.08-1.17) and the two highest quartile categories of AL and arthritis compared to the lowest quartile (quartile 3: OR=1.73, 95% CI=1.38-2.17, quartile 4: OR=1.79, 95% CI=1.41-2.26), after adjusting for confounders. The subscales of the inflammatory (OR=1.27, 95% CI=1.15-1.40) and metabolic system (OR=1.20, 95% CI=1.13-1.28) were also significant predictors. Conclusions: Cumulative biological risk is a plausible mechanism that is associated with arthritis.