Purpose: To compare the distribution of a p53 gene polymorphism among European subjects undergoing primary retinal detachment (RD) surgery in relation to the development of proliferative vitreoretinopathy (PVR). Design: Case-controlled gene association study conducted as a component of the Retina 4 Project (a European multicenter study). Participants and Controls: Five hundred fifty DNA samples, 134 with PVR secondary to primary RD and 416 with RD without PVR. Methods: The p53 codon 72 polymorphism (rs1042522) was analyzed using allele-specific primer polymerase chain reaction. Proportions of genotypes and the proline (Pro-P) homozygote groups between subsamples from different countries were analyzed in 2 phases. In the first, subsamples from Spain and Portugal were analyzed. After significant results were found, samples from the United Kingdom (UK)and The Netherlands were analyzed (second phase). Genotypic and allelic frequencies were compared betwee Main Outcome Measures: Single significant associations with PVR. Results: A significant difference (P < 0.05, Fisher exact test) was observed regarding the p53 genotype frequencies at codon 72 between the PVR cases and the non-PVR controls in Spain and Portugal (phase I), but not in the UK or The Netherlands (phase II). Analysis of Pro homozygote carriers between cases and controls revealed differences in Spain (29.01-42.18 and 2.29-10.20, respectively), Portugal (10.49-29.50 and 1.35-8.89, respectively), and The Netherlands (16.49-31.70 and 4.51-15.09, respe Conclusions: Results indicate that the Pro variant of p53 codon 72 polymorphism is associated with a higher risk of PVR developing after a primary RD. Further studies are necessary to understand the role of this polymorphism in the development of PVR. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013;120:623-628 (C) 2013 by the American Academy of Ophthalmology.