To evaluate whether the multidrug resistance gene 1 (MDR1) exon 26 polymorphisms are associated with the refractory rheumatoid arthritis (RRA). The study was carried out on two hundred and twenty-three patients with RA treated and one hundred and three normal controls. The RA treated were divided into two groups according the response to disease-modifying antirheumatic drugs (DMARDs). There were 108 patients in the effective group and 115 patients in the ineffective group. Genotypes of the C3435T polymorphism were determined by polymerase chain reaction followed by restriction digestion (PCR-RFLP). There were significant differences in the genotype frequency and allele frequency among three groups. Compared to responders and controls, the nonresponders carried more CC genotype (χ(2) = 5.306, P = 0.021; χ(2) = 7.810, P = 0.005) and more C allele (χ(2) = 6.601, P = 0.010; χ(2) = 12.172, P = 0.000). But, there were no statistically significant differences in genotype nor allele frequency between RA and healthy controls. The results from our study suggest that the C3435T MDR1 gene polymorphism may not be related with the RA susceptibility, but may influence the efficacy of RA therapy with DMARDs, and the 3435CC genotype may be related with RRA.