Objective.Neuropeptide S receptor 1 (NPSR1) is a G protein-coupled receptor involved in immune response and is associated with several inflammatory diseases. We investigated the possible contribution of several polymorphisms in the intronic region ofNPSR1to rheumatoid arthritis (RA).Methods.Genotyping of 7 single-nucleotide polymorphisms (SNP) was performed in a total of 1232 patients with RA and 983 healthy controls of Spanish white origin by real-time polymerase chain reaction technology, using the TaqMan 5′-allele discrimination assay.Results.One out of the 7 SNP analyzed (rs740347) was associated with RA [p after Bonferroni correction (pBNF) = 1.2 × 10−3, OR 0.73]. An association was also observed with rheumatoid factor-positive and shared epitope-positive RA (pBNF= 0.011, OR 0.73; pBNF= 0.037, OR 0.75, respectively).Conclusion.Our results show that variations in theNPSR1intronic region are associated with low risk in patients with RA, supporting other evidence that this locus represents a common genetic factor in inflammatory diseases.