Abstract Summary Higher levels of apolipoprotein A1 (ApoA1) were associated with higher risk of osteoporosis, which supports the argument that lipid metabolism is involved in bone metabolism. Background Although the current evidence shows that lipid metabolism and osteoporosis are closely related to cardiovascular disease, the association between ApoA1 and osteoporosis is still unknown. Therefore, the purpose of this study was to explore the relationship between ApoA1 and osteoporosis. Methods In this cross-sectional study, we included 7743 participants in the Third National Health and Nutrition Examination Survey. ApoA1 was regarded as an exposure variable and osteoporosis was considered as an outcome variable. Multivariate logistic regression analysis, sensitivity analysis, and receiver operator characteristic (ROC) were used to assess the association of ApoA1 with osteoporosis. Results Participants with higher ApoA1 had higher rates of osteoporosis compared to participants with lower ApoA1 (P