Progesterone and progesterone receptors (PGR) are known to play important roles in the pathophysiology of pelvic organ prolapse (POP). We investigated whether the PGR gene polymorphisms were associated with POP by conducting a case-control association study in 87 women with POP and 150 women without POP. Genotypes of the PGR gene polymorphisms (rs500760 and rs484389) were determined by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. There was significant difference between women with and those without POP in the distribution of the PGR rs484389 genotypes evaluated. Using multivariable logistic regression, older age, increased body mass index, menopausal status, and PGR rs484389 genotype CT were significantly associated with POP. The present study shows that PGR genotype may be associated with POP.