There are clinically relevant differences in symptomatology, risk stratification, and efficacy of therapies between men and women with coronary artery disease. Sex-based differences in plaque attenuation after administration of bone marrow mononuclear cells (BMNCs) are unknown. Forty-five male and 57 female apolipoprotein-E knockout (apoE^-/-) mice were fed a high-fat diet. At 14 weeks of age, animals received 4 biweekly intravenous sex-matched (males, n=11; females, n=13) or -mismatched (males, n=12; females, n=14) BMNCs obtained from C57BL6/J mice. The rest of the apoE^-/- mice were vehicle treated (males, n=13; females, n=20) or were age-matched untreated controls (males, n=9; females, n=10). Aortic plaque burden, progenitor cell profiles in bone marrow (BM) and 22 circulating cytokines/chemokines were examined 1 week following the final injection. Only female BMNCs infused into male apoE^-/- recipients significantly decreased plaque formation (P<0.001). This reparative response univariately correlated with increased CD34⁺ (P=0.02), CD45⁺ (P=0.0001), and AC133⁺/CD34⁺ (P=0.001) cell percentages in the BM of recipients but not with total serum cholesterol or percentage of BM-CD31⁺/CD45^low cells. In a multivariate analysis, BM-AC133⁺/CD34⁺ and BM-CD45⁺ percentage counts correlated with a lower plaque burden (P<0.05). Increased granulocyte colony-stimulating factor levels highly correlated with plaque attenuation (r=-0.86, P=0.0004). In untreated apoE^-/- mice of either sex, BM-AC133⁺/CD34⁺ cells rose initially and then fell as plaque accumulated; however, BM-AC133⁺/CD34⁺ percentages were higher in females at all times (P0.01). We have demonstrated an atheroprotective effect of female-derived BMNCs administered to male atherosclerotic apoE^-/- mice; this reparative response correlated with the upregulation of BM-AC133⁺/CD34⁺ and CD45⁺ cells and of circulating granulocyte colony-stimulating factor. Atherosclerotic female apoE^-/- mice did not exhibit atheroprotection after BMNCs of either sex. Our findings may have implications for clinical cell therapy trials for coronary artery disease. Further exploration of sex-based differences in atheroprotection and vascular repair is warranted.