Although the importance of glycoprotein Duffy in the human red cells invasion process by Plasmodium vivax merozoites has been demonstrated, little is known about the associations of FY polymorphisms with malaria vivax parasitic density. In this study, we investigated the associations of the SNPs 125 G>A, 265 C>T, and 298 G>A on FY gene and the SNP -33T>C on GATA box with the vivax malaria parasitic density in inhabitants of Amazon State, Brazil. Verifications of P. vivax, as well as the definition of parasitism, were determined by standard screening tests in 497 patients. FY phenotyping was performed in all samples by hemagglutination using gel cards. Molecular analysis for FY/GATA polymorphisms were performed by polymerase chain reaction-restriction fragment length polymorphism. Our data showed that in this population, FY*A/FY*B-33 and FY*B/FY*B-33 genotypes may be a selective advantage, reducing the frequency of P. vivax infection in the studied area. FY*A/FY*B and FY*A/FY*A genotypes showed to be associated with the rise of the frequency of P. vivax infection, and FY*B/FY*X and FY*A/FY*X showed to be associated with the low levels of parasitism. These results suggest that natural adaptations, in malaria-endemic regions, could be leading to the arising of partial defense mechanisms against P. vivax, which is different from the previously described in African descents, as well as adaptations that could be increasing the susceptibility of human to this kind of malaria.