Purpose: The presence of pathogenic microorganisms associated with both chronic periodontitis and implant failure can induce a host immune response. The type of response is determined by an individual's genetic makeup. The aim of this study was to investigate the genetic relationship between interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α) polymorphisms and patient susceptibility to chronic periodontitis or implant failure and to compare their immunogenetic functions. Materials and Methods: This study recruited subjects according to clinical diagnostic criteria for failing implants, chronic periodontitis, healthy implants, and healthy controls. Human DNA from buccal swabs was analyzed by amplification refractory mutation system-polymerase chain reaction and agarose gel electrophoresis performed for gene polymorphisms of IL-10 (IL-10, IL-1082, IL-819, and IL-592) and TNF-α (TNF-α-308). Differences in the polymorphisms between test groups and healthy controls were assessed by Pearson chi-square test. Results: A total of 95 patients (16 failing implants, 22 chronic periodontitis, 23 healthy implants, and 34 healthy controls) were enrolled in this study. No significant association of IL-10 and TNF-α alleles, genotypes, or haplotypes were observed in chronic periodontitis or failing implant patients (P > .005). However, both patient groups showed highly similar frequencies of alleles, genotypes, and haplotypes (P > .99). Conclusion: This study found no significant association of either IL-10 or TNF-α genes in the susceptibility to the development of chronic periodontitis or implant failure. Keywords: chronic periodontitis, cytokines, failing implants, interleukin-10, single nucleotide polymorphisms, tumor necrosis factor-alpha