Problem Association between PAI-1 4G/5G polymorphism and reproductive failures has been postulated. We aimed to investigate its impact on metabolic, hormonal, and immune profiles of women with reproductive failures. Method of study A retrospective study was carried out in 208 women with a history of reproductive failure. Study patients were divided into three groups: women with repeated implantation failure ( RIF, n = 40), recurrent pregnancy loss ( RPL, n = 113), and both RIF and RPL ( n = 55). Fertile controls were 92. Results PAI-1 4G/4G was prevalent in RPL, RIF, and RIF/ RPL groups when compared with controls ( P = 0.003) and associated with increased risks of RIF, RPL, and RIF with RPL ( OR = 4.5, 2.2 and 2.7). Women with PAI-1 4G/4G have significantly higher BMI, glucose, and PAI-1 levels and lower NK cytotoxicity when compared with women without PAI-1 4G/4G. Conclusion PAI-1 4G/5G polymorphism plays a major role in the pathogenesis of RPL and RIF by altering metabolic and immunological profiles. [ABSTRACT FROM AUTHOR]