Ankylosing spondylitis (AS) is a chronic inflammatory disease in which genetic factors play a central role. The efficacy of TNF blockers has reoriented research in this field in order to explain the influence of TNF in AS pathogenesis. The objective of this study was to access the influence of single nucleotide polymorphisms (SNPs) at positions -308 and -238 of the promoter region of TNF gene on AS susceptibility and prognosis. SNPs were determined by restriction fragment length polymorphisms in patients and controls. AS patients exhibited a decreased frequency of the A allele at position -238 (10%) when compared with controls (18%), suggesting that this could be a protective factor for disease susceptibility. In addition, the -308 GA/AA genotypes were associated with later disease onset in AS patients. These results suggest that TNF gene promoter polymorphisms at positions -238 and -308 could have a small influence on AS susceptibility and prognosis.