AbstractSeveral but not all studies have provided evidence for the association between multiple sclerosis (MS) and the T244I variant of the interleukin‐7 receptor‐alpha gene (IL7RA), rs6897932. We performed a new replication case–control study in 599 MS patients and 594 healthy controls, all Caucasians from the south of Spain. The genotype and allele frequencies differed between MS cases and controls. The IL7RA rs6897932 C allele and the CC genotype were found to be factors for disease susceptibility [per allele odds ratio (OR) 1.32, 95% CI 1.1–1.6, P = 0.0031; per CC genotype vs TT + TC genotypes, OR 1.5, 95% CI 1.18–1.87, P = 0.0007]. The combined data analysis included 3324 cases and 5032 controls of Europeans and Americans of European origin resulting in stronger association with similar OR (P = 1.9 × 10E−9). These findings in our sample support previous reported association studies between IL7RA rs6897932 and MS.