: Arthritis is a prevalent condition posing a significant threat to human health. The lactate dehydrogenase to albumin ratio (LAR) has been recognized as a key indicator for the onset and progression of various diseases. However, its association with arthritis remains incompletely investigated. This cross-sectional study analyzed data from adult participants in the National Health and Nutrition Examination Survey (1999–2010). Arthritis identification was based on self-reported information. We employed weighted logistic regression analysis to assess the odds ratio (OR) and 95% confidence interval (CI) for the association between log ₂ -transformed LAR (log ₂ (LAR)) and arthritis. We also employed subgroup and sensitivity analyses to evaluate the robustness of results. Among 8616 participants, 2229 had arthritis. After full covariate adjustment, log ₂ (LAR) was significantly associated with arthritis (OR: 1.52; 95% CI: 1.16–2.01; P = .003). Participants in the highest log ₂ (LAR) quartile had a 37% higher arthritis risk versus the lowest quartile (adjusted OR: 1.37; 95% CI: 1.07–1.74; P = .013). Subgroup and sensitivity analyses confirmed result stability. Elevated log ₂ (LAR) levels were associated with increased risk of arthritis (OR: 1.52; 95% CI: 1.16–2.01; P = .003).