Recent genome-wide association studies have provided evidence for the involvement of 3p21 in the pathogenesis of Crohn's disease (CD). Here we attempted to validate the 3p21 region in a well characterized CD case-control New Zealand dataset of 329 CD patients and 521 controls by genotyping tagging single nucleotide polymorphisms (SNPs) across this region. Analysis revealed significant differences between patients and controls for six of 14 SNPs: rs9874472, rs1800668, rs11716445, rs4283605, rs2131109, and rs6446298. Five of these demonstrated strong interaction with CARD15 and phenotypic analysis demonstrated association of these SNPs with age at first diagnosis, CD location, CD behavior and requirement of bowel resection. The results from this study support the accumulating evidence that suggests the 3p21 region is a CD-associated locus, although it remains unclear which is the causative SNP and/or gene.