ObjectivesVitamin A plays an important role in health, especially regarding its impact on bone tissue. Vitamin A can lead to bone damage and deformity, thus becoming an important causative factor in osteoarthritis. In this study, we aimed to evaluate the association of serum vitamin A with osteoarthritis.MethodsWe included participants who self-reported whether they had OA in NHANES 2001–2006 and NHANES 2017–2018 to explore the association and dose–response relationship between vitamin A concentration and risk of osteoarthritis through weighted multivariate logistic models and restricted cubic splines. Sensitivity and stratification analyses were also used to assess the robustness of the results.ResultsA total of 18,034 participants were included in this study, and a linear association between serum vitamin A concentration and osteoarthritis risk was observed. The OR of osteoarthritis was 1.22 (95% CI: 0.98, 1.52), 1.40 (95% CI: 1.05,1.85), and 1.47 (95% CI: 1.14, 1.91) for participants in the second, third, and fourth quartiles, respectively, compared with the lowest vitamin A reference group. Similar results were obtained when sensitivity and stratification analyses were performed.ConclusionSerum vitamin A is positively associated with osteoarthritis risk. Within a certain range of vitamin A concentrations, vitamin A is a protective factor against osteoarthritis, beyond which it becomes a causative factor for osteoarthritis.