Objective: Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases, with a multifactorial etiopathogenesis, an interaction between predisposing factors and/or systemic conditions and immunological components in genetically predisposed subjects. Although there is no clear genetic mode of inheritance, there is evidence that inheritance of specific gene polymorphisms may predispose individuals to RAS. The purpose of the present study was to investigate a possible association between the functional interleukin 4 (IL4) VNTR genetic polymorphism and RAS in a sample of Turkish patients. Methods: The study included 145 unrelated patients with a clinical diagnosis of RAS and 150 unrelated healthy controls. Genomic DNA was isolated and IL4 gene 70. bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers. Results: The distribution of genotype and allele frequencies of IL4 gene intron 3 VNTR polymorphism was statistically different between RAS patients and control group (p < 0.0001 and p < 0.0001, respectively) P2P2 genotype and P2 allele were also found to be protective with a lower risk for susceptibility to RAS (p < 0.0001). Conclusion: The results of this study suggest that intron 3 VNTR polymorphism in the IL4 gene is associated with RAS susceptibility in Turkish population. © 2013 Elsevier B.V.