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Abstract Background Excessive exposure to heavy metals has been linked to various health problems, including organ damage, neurological disorders, and reproductive and developmental abnormalities. However, the relationship between heavy metals exposure and uterine fibroids remains uncertain. To explore this association, we conducted a cross-sectional study among American women. Methods We utilized data from three cycles of the National Health and Nutrition Examination Survey (NHANES, 1999–2006) to evaluate the association between uterine fibroids and blood heavy metal levels, including lead (Pb), cadmium (Cd), and mercury (Hg). Weighted logistic regression, restricted cubic spline (RCS), Bayesian kernel machine regression (BKMR), and subgroup analyse were used to examine the potential relationships between blood heavy metals and uterine fibroids. Results Of the 4502 American women studied, 542 (12.04%) had uterine fibroids. Elevated levels of all heavy metals were significantly more common in women with uterine fibroids (P