Ankylosing spondylitis (AS) is an inflammatory arthritis, which affects mainly spine and sacroiliac joints. According to recent studies, ERAP1 is the second most common candidate gene for AS susceptibility after HLA-B27. The aim of this study was to determine the association of ERAP1 gene polymorphisms with AS in Iranian population.The study group comprised 387 Iranian AS patients and 316 healthy controls from Iran. Using Real Time PCR allelic discrimination method, we genotyped four SNPs (rs30187, rs469876, rs13167972 and rs27434) of ERAP1. We found that rs30187 and rs27434 were significantly associated with AS in Iranian population (P=6×10-5, P=7×10-3, respectively). The rs30187 T/T genotype was associated with AS compared with C/C genotype (P=1.5×10-5). The rs27434 G/G genotype was inversely associated with AS (P=5×10-3). Two specific haplotypes including: rs30187/ rs469876/ rs13167972/ rs27434 TAAA and CAGG were associated with increased and decreased risk of AS in Iranian population, respectively. These results indicated that ERAP1 SNPs and haplotypes were associated with AS in Iranian population.