Background: Based on its function in immune response tumor necrosis factor-alpha (TNFa) has been regarded as a candidate gene for inflammatory diseases, including periodontal disease and Crohn's disease (CD). However, the results regarding the impact of genetic characteristics of TNFa on both diseases are inconsistent. The present study was performed in order to evaluate the influence of TNFa polymorphisms as potential risk factors for Crohn's disease after stratification according to periodontal status. Patients and methods: A total of 142 patients with Crohn's disease were included in the study. Genotypes, alleles and haplotypes of TNFa SNPs (rs1800629: c.-308G>A and rs361525: c.-238G>A) were determined by polymerase chain reaction with sequence-specific primers (PCR-SSP). Statistical analyses were performed applying SPSS 19.0. Results: Patients with Crohn's disease suffering from generalized periodontitis were significantly more often carriers of AA-genotype and A-allele of rs1800629 than Crohn's patients without generalized periodontitis (genotype: pexact=0.044, allele: pcorr.=0.048). In binary logistic regression analyses considering age, gender, smoking, approximal plaque index as potential confounders significant allele- but no genotype-dependent associations were proven (OR=2.22). Evaluating the TNFa polymorphism rs361525 no disease related differences in genotype or allele arrangement could be detected. Conclusions: TNFa polymorphism rs1800629 but not rs361525 was proven to be a significant risk indicator for generalized periodontitis in patients with Crohn's disease. Keywords: SNPs, TNFa, Crohn's disease, periodontitis