Aims/Purpose: The TP53 Arg72Pro polymorphism has been linked to the risk of proliferative vitreoretinopathy (PVR) and may alter the functional prognosis of individuals with retinal detachment (RD). The current study aims to determine the effect of the TP53 Arg72Pro variant on inflammation and apoptosis following RD.Methods: Sixty patients undergoing RD surgery were included in the study. Using the PCR‐RFLP method, the TP53 Arg72Pro polymorphism was identified in peripheral blood. A RD model was also performed in humanized TP53 Arg72Pro KI mice. In human and animal retinal tissues, mRNA expression for genes involved in inflammation and apoptosis were examined using comparative quantitative PCR (qPCR). Immunohistochemistry was performed to study the presence of glial fibrillary acidic protein (GFAP) in the mouse retina. For statistical analysis, the SPSS v15 program was employed.Results: After RD, mice with the proline mutation exhibited increased expression of the inflammatory genes TGFB1, IL1 and IL6. Additionally, after RD, the immunoexpression of retinal GFAP was also raised in the Pro variant. Carriers of the Arg/Arg mutation displayed an increase in the relative mRNA expression of the BAX and CASP3 intrinsic apoptotic genes in retinal tissue after RD in patients and mice model.Conclusions: The human TP53 Arg72Pro genetic variant has been linked to inflammation and retinal cellular death after RD, suggesting that it could be a genetic biomarker for RD prognosis.Funded: Ministerio de Ciencia e Innovación (Spain Government) (PID2020‐114585RA‐I00).