Involvement of genetic factors in the aetiology of inflammatory bowel disease (IBD) has been known for a long time. Our aim was to investigate the prevalence of polymorphisms in NOD2, ICAM-1 and CCR5 genes in Czech and Slovak patients with IBD in comparison with healthy controls. The frequency of well-known mutations (R702W, G908W and 1007fs in the NOD2 gene; K469E in the ICAM-1 gene, and Delta32 in the CCR5 gene) involved in IBD was tested in 45 patients with CD and 22 patients with UC. The allele frequency of these mutations was determined and genotype-phenotype correlation was specified. Isolated DNA was genotyped, and allele frequency was counted and statistically verified. Significant differences between the healthy control group and CD patients were observed in mutation 1007fs of the NOD2 gene (P = 0.0203). We also associated allele E469 of the ICAM-1 gene with CD (P = 0.0024). No significant association between other alleles and CD was found, and no gene variation was linked to UC. The number of mutations and mutated genes was higher among patients with CD than among patients with UC. Our results support previous findings about participation of mutations of NOD2 and ICAM-1 genes in IBD. We confirmed that both CD and UC are polygenic diseases with a genedosage effect. This observation strengthens the opinion that genetic factors play a more important role in CD than in UC.