Purpose: Receptor activator for nuclear factor kappa B ligand (RANKL)/RANK/OPG pathway plays a redundant role in osteoclastogenesis, osteoclast activation and regulation of bone resorption. Recently, single nucleotide polymorphisms (SNP) have been reported as a co-factor in pathogenesis of inflammatory diseases. The aim of this study was to investigate the relationship between osteoprotegerin (OPG) gene polymorphisms and chronic periodontitis and peri-implantitis in an Iranian population. Materials and methods: 77 patients with chronic periodontitis (CP), 40 patients with peri-implantitis (PI) and 89 periodontally healthy subjects were enrolled in this study. A total of 5 ml of blood was obtained from the arm vein of participants. DNA was extracted based on the salting out method. Two functional SNPs (T950C and G1181C) were analysed by using polymerase chain reaction and restriction fragment length polymorphism (PCR_RFLP). The prevalence differences in three batches were evaluated by chi-square test. Results: An evaluation of the T950C genotype found that there was no statistical difference between groups. A comparison of the G1181C genotype distribution between peri-implantitis and chronic periodontitis groups, and between peri-implantitis and normal groups found that the frequency of the CC genotype was significantly higher in patients with peri-implantitis (P = 0.005). Conclusions: Our results indicate that a SNP at G1181C is associated with the presence of PI. Keywords: gene polymorphism, osteoprotegerin, peri-implantitis, periodontitis