Background: Half of the cases of vision loss in people under 60 years of age have been attributed to age-related macular degeneration (AMD). This is a multifactorial disease with late onset. It has been demonstrated that many different genetic loci are implicated in the risk of developing AMD in different populations. In the current study, we investigated the association of high temperature requirement A-1 (HTRA1) gene polymorphisms with the risk of developing AMD in the Iranian population.Methods: Genomic DNA samples were extracted from 120 patients with AMD and 120 healthy ageand sex-matched controls. A 385 base-pair fragment of the HTRA1 gene promoter region was amplified using the polymerase chain reaction (PCR) technique and sequenced. The frequencies of the alleles were calculated and statistical analysis was performed using SPSS software.Results: Our study demonstrated that the rate of polymorphisms rs11200638 -625 G>A and rs2672598 -487T>C were significantly greater in AMD patients than in healthy controls from the Iranian population.Conclusions: The results of our study indicate that HTRA1 gene promoter region polymorphisms are associated with the risk of developing AMD in the Iranian population.