Background: A functional polymorphism located at 21 from the start codon of the CD40 gene, rs1883832, was previously reported to disrupt a Kozak sequence essential for translation. It has been consistently associated with Graves’ disease risk in populations of different ethnicity and genetic proxies of this variant evaluated in genome-wide association studies have shown evidence of an effect in rheumatoid arthritis and multiple sclerosis (MS) susceptibility. However, the protective allele associated with Graves’ disease or rheumatoid arthritis has shown a risk role in MS, an effect that we aimed to replicate in the present work. We hypothesized that this functional polymorphism might also show an association with other complex autoimmune condition such as inflammatory bowel disease, given the CD40 overexpression previously observed in Crohn’s disease (CD) lesions. Methodology: Genotyping of rs1883832C.T was performed in 1564 MS, 1102 CD and 969 ulcerative colitis (UC) Spanish patients and in 2948 ethnically matched controls by TaqMan chemistry. Principal Findings: The observed effect of the minor allele rs1883832T was replicated in our independent Spanish MS cohort [p= 0.025; OR (95% CI)= 1.12 (1.01–1.23)]. The frequency of the minor allele was also significantly higher in CD patients than in controls [p= 0.002; OR (95% CI)= 1.19 (1.06–1.33)]. This increased predisposition was not detected in UC patients [p= 0.5; OR (95% CI)= 1.04 (0.93–1.17)]. Conclusion: The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions ; Formal Correction: This article has been formally corrected to address the following errors. The values in the first column of table 1 were published incorrectly. Please view the corrected table here:http://www.plosone.org/annotation/listThread.action?inReplyTo=6983&root=6983 ; This work was supported by grants from: “Fundación Mutua Madrileña”, “Fundación Ramón Areces”, Junta de Andalucía-Feder P07-CVI-02551, Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (Feder) (PI081636, PI081676, PI070353 and RETICS-REEM RD07/0060) and Ministerio de Ciencia e Innovación-Feder (SAF2009-11491, SAF2006-00398). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.