Objective: To evaluate the association between endometriosis and the p53 polymorphism. Design: Prospective study. Setting: Department of gynecology and genetics in a medical center. Patient(s): Women with and without endometriosis. Intervention(s): Women were categorized as having moderate or severe endometriosis (n = 118) or no endometriosis (n = 140). Main Outcome Measure(s): Polymerase chain reaction was used to detect p53 codon 72 polymorphisms (arginine homozygosity, heterozygosity, and proline homozygosity). Associations between endometriosis and p53 polymorphisms were evaluated. Result(s): The distributions of different p53 polymorphisms differed significantly between groups. The respective proportions of arginine homozygotes, heterozygotes, and proline homozygotes were 10.2%, 66.9%, and 22.9% in the group with endometriosis and 30.7%, 50%, and 19.3% in the group without endometriosis. Conclusion(s): Endometriosis is associated with p53 polymorphism. p53 arginine homozygotes have lower risk for endometriosis. Heterozygotes and proline homozygotes have higher risk for endometriosis.