Arterial disease is associated with elevated serum matrix metalloproteinase (MMP)-8 concentration. We studied the role of two promoter region single nucleotide polymorphisms (SNPs) of MMP-8 gene in the arterial disease. The population comprised patients with arterial disease ( n = 124) and healthy blood donors ( n = 100) as a reference group for MMP-8 SNPs (−799C/T and −381A/G) genotypes and serum concentrations. Genotype frequencies for MMP-8 −799C/T SNP in arterial disease were C/C (43.5%), C/T (32.3%) and T/T (24.2%), and in the reference group they were C/C (50.0%), C/T (40.0%) and T/T (10.0%; P = 0.012). The −799C allele frequency was lower in the patients (59.7%) than in the reference group (70.0%; P = 0.023). The −799C allele showed protective effects against the arterial disease with an odds ratio [95% confidence interval (CI)] of 0.372 (0.141–0.980, P = 0.045) after adjustment for age, gender, and serum MMP-8 and TIMP-1 concentrations. Only in the reference group and whole study population ( n = 224), the −799TT genotype significantly associated with an increase in serum MMP-8 concentrations ( P = 0.047, 0.025). The −799C allele appeared protective against the arterial disease. The genotype may have an effect on systemic MMP-8 levels which could not, however, be seen in the arterial disease patients probably as a result of the strong inflammation involved in the disease pathogenesis.