Aim: PGE2 has been reported to be associated with periodontal attachment loss and alveolar bone resorption, which suggests that PGE2 is involved in the pathogenesis of periodontal disease. Among the receptors of PGE2, EP4 receptor  regulate inflammatory and immunological responses in periodontal lesions. The present study was aimed at evaluating a possible association of single nucleotide polymorphism of PGE2 EP4 receptor gene with susceptibility and severity of chronic and aggressive periodontitis. Materials and Methods: A total of 105 subjects were divided into 3 groups of 35 patients each and grouped as Group I– 35 Healthy controls, Group II– 35 Chronic periodontitis patients, Group III– 35 Aggressive periodontitis patients. 2ml of blood sample was collected from all the subjects and subjected to assessment of polymorphism of PGE2 EP4 receptor using polymerase chain reaction technique.The analysis of variance (ANOVA) and chi–square test was used to analyze the genotype distribution among chronic, aggressive periodontitis patients and healthy controls. Results: Significant differences were found between the frequency of PGE2 EP4 receptor genotypes in periodontitis group and control group. CC and GC genotype were more prevalent in aggressive, chronic periodontitis patients and GG genotype was prevalent in healthy controls. Conclusion: The GC and CC genotype of PGE2 EP4 receptor genetic polymorphism may increases the susceptibility to chronic and aggressive periodontitis respectively and that the GG genotype found in healthy controls may protect against periodontitis.