Background/Aim: The TP53 tumor suppressor gene encodes the nuclear phosphoprotein p53, which plays an important role in cell cycle regulation, apoptosis, DNA repair and angiogenesis. The TP53 gene contains common genetic polymorphisms that influence gene activity. Clinical implications of TP53 polymorphisms have been reported for several diseases, including a variety of solid tumors and endometriosis. We evaluated the association of a TP53 duplication polymorphism with endometriosis. Methods: We evaluated the role of the TP53 16-bp duplication polymorphism by comparing the genotypes of 204 healthy women (controls with surgically excluded endometriosis) to the genotypes of 151 women with endometriosis in the Mexican population. Results: The observed genotype frequencies for controls and endometriosis patients were 0.5 and 5% for 16 bp+/+, 11 and 21% for 16 bp+/–, and 88.5 and 77% for 16 bp–/–, respectively. The odds ratio (OR) was 9.8 (95% CI 1.2–446.8; p = 0.01). The association was more evident when we compared the distribution of genotype 16 bp+/+ to genotype 16 bp+/–. In patients with moderate/severe endometriosis, the OR was 4.0 (95% CI 1.6–9.8; p = 0.003). Conclusion: Our data suggest that the 16-bp duplication polymorphism in TP53 contributes significantly to endometriosis susceptibility in the Mexican population.