Renin-angiotensin system (RAS) polymorphisms have been studied as candidate risk factors for hypertension with inconsistent results, possibly due to heterogeneity among various genetic and environmental factors. A case-control association study was conducted to investigate a possible involvement of polymorphisms of three RAS genes: AGT M235T (rs699), ACE I/D (rs4340) and G2350A (rs4343), and AGTR1 A1166C (rs5186) in essential hypertensive patients. A total of 211 cases and 211 controls were recruited for this study. Genotyping was performed using PCR-RFLP method. The genotype and allele distribution of the M235T variant differed significantly in hypertensives and normotensives (OR-CI = 2.62 (1.24-5.76), P = 0.006; OR-CI = 0.699 (0.518-0.943), P = 0.018), respectively. When the samples were segregated based on sex, the 235TT genotype and T allele were predominant in the female patients (OR-CI = 5.68 (1.60-25.10), P = 0.002; OR-CI = 0.522 (0.330-0.826), P = 0.005) as compare to the male patients (OR-CI = 1.54 (1.24-5.76), P = 0.34; OR-CI = 0.874 (0.330-0.826), P = 0.506), respectively. For ACE DD variant, we found overrepresentation of "I"-allele (homozygous II and heterozygous ID) in unaffected males which suggest its protective role in studied population (OR-CI = 0.401 (0.224-0.718); P = 0.0009). The M235T variant of the AGT is significantly associated with female hypertensives and ACE DD variant could be a risk allele for essential hypertension in south India.