Purpose: Tumor necrosis factor-alpha (TNFa) is a proinflammatory cytokine, which promotes bone resorption and mediates the inflammatory response to infection. Because implant failures appear to cluster in subsets of individuals, this phenomenon may be related to gene polymorphisms. Therefore, the aim of this study was to investigate the relationship between a specific polymorphism in the TNFa gene (allele 2 of TNFa-308) and peri-implantitis. Materials and Methods: This case-control study included Caucasian nonsmoking Brazilian patients with implant-supported restorations. Oral epithelial cells were taken from patients with and without peri-implantitis to evaluate the frequencies of different alleles of the TNFa-308 gene by polymerase chain reaction. Results: Ninety patients (49 with peri-implantitis and 41 with healthy implants) were enrolled in this study. Polymorphism in allele 2 of TNFa-308 was not associated with an increased risk for peri-implantitis (P = .8171), although 14.63% of the subjects in the control group carried allele 2 and 19.39% in the peri-implantitis group carried allele 2 (chi-squared = 0.708; P = .5202). Conclusion: Polymorphism of the TNFa-308 gene was not associated with an increased risk of peri-implantitis in the population evaluated in this study. Keywords: bone loss, dental implants, gene polymorphisms, peri-implantitis, tumor necrosis factor-alpha