Objective: To study the efficacy and safety profile of Telmisartan 40 mg and Azilsartan 40 mg in stage I systemic Hypertension among patients attending cardiac OPD in a tertiary care center. Methods: An open-labeled comparative study was conducted in the Department of Cardiology, Osmania General Hospital, Hyderabad, for 24 mo. All patients with stage I systemic hypertension of either sex, aged 18-65 y, with blood pressures of >140/90 mmHg and/or diabetes mellitus attending the cardiac outpatient department at Osmania General Hospital. After initial screening, diagnosed cases of essential hypertension were randomly allocated to either group 1 (Tablet Azilsartan 40 mg or group 2 (Tablet Telmisartan 40 mg). The patients were advised to report for follow-up for review on the 4th, 8th, 12th, and 24th week. Results: The mean decrease in the systolic blood pressure in both groups was statistically significant with a P value of<0.05 at the 8th week, 12th week, and the end of the 24th week. The mean decrease in diastolic blood pressure in both groups was statistically significant with a P value of 0.01 at the end of the 24th week. The difference between the SBP and DBP at various intervals is statistically significant with an Anova P value of<0.0000001. Conclusion: Both drugs controlled blood pressure at similar proportions. However, the mean of SBP and DBP for the Azilsartan group was lower than the Telmisartan Group. Both drugs were tolerated well, and no significant adverse effects were noted during the study.