Various genes that may influence the intestinal barrier have been identified, including MAGI2, PARD3, and MYO9B. These genes are associated with inflammatory bowel disease (IBD) in several European studies. A total of 2,049 individuals (656 Crohn's disease [CD], 544 ulcerative colitis [UC], and 849 controls) were genotyped and association studies were performed for 1 single nucleotide polymorphism (SNP) in MAGI2, 1 SNP in PARD3, and 6 SNPs in MYO9B. We reported an association between 3 SNPs in MYO9B and ileal involvement with rs1457092 as the most significant SNP (p = 0.0073, odds ratio [OR] 0.69 [95% confidence interval (95% CI) 0.52-0.90]). The nonsynonymous SNP rs1545620 exhibited a p value of 0.014, OR 0.72 (95% CI 0.55-0.93). MYO9B was not associated with UC. MAGI2 or PARD3 was not associated with IBD. A 6-SNP haplotype block in MYO9B demonstrated association with CD and ileal CD (p = 0.0030 and 0.0065, respectively). These data demonstrate an association of MYO9B with ileal CD; however, there was no association of MAGI2 and PARD3 with IBD. Because the direction of association of MYO9B in this Canadian study was not consistent with European studies, further studies are needed to elucidate the role of MYO9B in IBD.