Genetic, environmental and demographic factors contribute to the development of essential hypertension. Genetic polymorphism of Rennin-angiotensin-aldosterone system (RAAS) has been extensively studied to determine the genetic susceptibility to hypertension. The insertion/deletion (I/D) angiotensin converting enzyme (ACE) polymorphism has been established as a cardiovascular risk factor in some population, but its association with essential hypertension is controversial. This study sought to determine the association of I/D polymorphism of the ACE gene in south Indian essential hypertensive subjects. A total of 208 clinically diagnosed essential hypertensive patients without any associated diseases and 220 healthy control subjects were included in this study. Distribution and allelic frequency of Insertion (I) and Deletion (D) polymorphism at the 287 base pair Alu repeat sequence in the intron 16 of ACE gene were analyzed. The distribution of II, ID, DD genotypes of ACE gene was 28.3%, 32.6% and 38.9% respectively in essential hypertensive patients and to 53.6%, 26.3% and 20% in controls. The allele frequency for D allele is 0.58 in essential hypertension as compared to 0.34 of control subjects. The genotype and allele frequency of ACE gene polymorphism is significantly differed in patients when compared to controls. In conclusion, the I/D polymorphism of ACE gene is associated with Indian essential hypertension.