Understanding the pathogenesis of Plasmodium vivax malaria is challenging. We hypothesized that susceptibility to P. vivax-induced thrombocytopenia could be associated with polymorphisms on relevant platelet membrane integrins: integrin ?2 (C807T), and integrin ?3 (T1565C). Although ?3 polymorphism was not related with P. vivax malaria, ?2 807T carriers, which show high levels of integrin ?2?1, had a higher probability for severe thrombocytopenia than wild-type carriers. This evidence of the association of integrin polymorphism and P. vivax morbidity was further demonstrated by a moderate but significant correlation between clinical disease and surface levels of the integrin ?2?1.