The TNF-α gene has been associated with a number of autoimmune diseases, including RF. In our study, we investigated if the G-238A and G-308A polymorphisms of TNF-α gene are associated with RF and RHD in a cohort of 71 patients and 50 healthy controls (HC). All cases showed a significantly higher frequency of 308A allele (OR=4.65; P= 0.0001), and homozygous genotypes 308 AA (OR=18.04; P=0.0001). On the other hand, all cases showed a significantly increased frequency of 238A allele (OR=1.84; P=0.04), with non-significantly increased homozygous genotypes 238 AA (OR=3.08; P=0.074). In conclusion, we show that the TNFA is a susceptibility locus for RF and RHD that may have therapeutic, economic and social implications.