Hemophilia A is an X-linked bleeding disorder caused by mutations in the FVIII gene. BrazIT is a nationwide cohort of 193 patients that, developing neutralizing alloantibodies (inhibitors) against the first line treatment with exogenous FVIII, received Immunotolerance Treatment (ITI). Sixtyseven patients (35%) failed ITI, 62 (32%) achieved partial success, and 64 (33%) had complete success. We performed whole exome sequencing of BrazIT and estimated medians of 64%, 17%, and 13% of European, African, and Native American ancestries, respectively, based on autosome SNVs, underscoring the diversity of this cohort. After controlling for covariates, we did not observe association between these continental ancestries and inhibitor titers or ITI success, but Native American ancestry was negatively associated with large deletions in FVIII gene (β = -0.081, p = 0.011). In Latin American populations, sex-ancestry bias is the rule: during the last five centuries, European admixture has been preferentially mediated by males, while African and Native American admixture preferentially by females. We estimated X-chromosome ancestry to confirm the pervasive sex-ancestry bias in BrazIT. As expected, BrazIT individuals show Native American ancestry bias (Autosome - X-chromosome bias: 0.06, p < 0.001), but exceptionally, no African ancestry bias (-0.005, NS). This result suggests that X-chromosomes of predominant African origins are underrepresented among hemophilia patients high-responding inhibitors, exemplifying the unexplored issue of how sex-ancestry bias in Post-Columbian migrations from Europe and Africa to the Americas have differently shaped the patterns of genetic diversity of X-chromosome and autosomal linked mendelian diseases.