Background: Essential hypertension is among such lifestyle diseases which are the leading causes of premature deaths around the globe, due to their cardiovascular and kidney disease complications, if remains untreated. Angiotensin converting enzyme gene I/D polymorphism has been found to affect hypertension and the response of antihypertensive therapies. Materials and Methods: This is prospective and cross-sectional study. In Group – A: ACE gene polymorphism in hypertension a) Azilsartan (40-80mg) b) Atenolol (25-100mg) c) Chlorthalidone (12.5-25mg) Result: In our study baseline, systolic blood pressure was 172.31 mmHg Atenolol group, 179.94 mmHg Azilsartan group and in Chlorthalidone was 177.48 mmHg. Baseline Diastolic Blood pressure was 101.43 mmHg in Atenolol group, 103.78 mmHg in Azilsartan group and in Chlorthalidone was 109.59 mmHg. While comparing among 3 groups baseline blood pressure was statistically not significant. After 3 months of treatment with Atenolol group, 163.42 mmHg, in Azilsartan group 167.47 mmHg and in Chlorthalidone was 169.47 mmHg systolic blood pressure. Baseline Diastolic Blood pressure was 98.48 mmHg in Atenolol group, 97.58 mmHg in Azilsartan group and in Chlorthalidone was 98.37 mmHg. While comparing among 3 groups after 3 months blood pressure was statistically significant. Conclusion: Angiotensin Converting Enzyme (ACE) gene polymorphism is linked to isolated systolic hypertension (ISH). Renin-Angiotensin-Aldosterone-System (RAAS) is one of the regulatory systems governing circulation, systemic vascular resistance, and kidney function.