Abstract Purpose Age‐related macular degeneration (AMD) is a leading cause of visual impairment in developed countries, particularly in the Caucasian population above 65 years. It is a complex disorder with both genetic and environmental factors playing a role. Variants of HTRA serine peptidase 1 gene (HTRA1), particularly a single nucleotide polymorphism (SNP) in its 5’ regulatory region –512G>A (rs11200638), is among those most strongly associated with AMD susceptibility but so far its frequency has not been analyzed in the Polish population. The purpose of this study was to investigate the association of rs11200638 with AMD in Polish patients. Methods AMD patients (n=140) and age‐matched controls (n=162) were enrolled in the study. Total genomic DNA was isolated from blood and rs11200638 was genotyped in both groups by restriction fragment length polymorphism (PCR‐RFLP) analysis using MspI endonuclease and direct sequencing. PCR primers were designed based on the reference sequence of the gene (AF157623). Allele and genotype frequencies were compared between the groups by Chi square test and odds ratio (OR) with 95% confidence intervals (95% CI) were calculated to estimate risk. Results Frequencies of the GG, GA and AA genotypes were 52%, 33% and 15% in control subjects and 28%, 15% and 57% in AMD patients, respectively. The AA genotype was significantly more prevalent in patients with AMD than among control subjects (OR= 7.7, 95%CI: 4.4‐13.2, Chi square 53.6, P<10‐6). Conclusion In the present study, polymorphic variant of HTRA1 gene (rs11200638) showed strong association with AMD, verifying its significant role as a disease susceptibility gene also in Polish patients.