Background: Recent guidelines have suggested combination therapy as initial treatment in hypertensive patients with ≥ grade 2 hypertension, aiming to achieve target blood pressure (BP) goal faster and more effectively. Both calcium channel blockers (CCBs) and angiotensin converting enzyme inhibitors (ACEIs) are in the list of first-line antihypertensives, however the choice of the combination therapy is left to the discretion of the clinician, and there are concerns that ACEIs are less effective in BP reduction among black hypertensives. We aimed to study the BP lowering effect after 4 weeks of treatment with Amlodipine (CCB) and Lisinopril (ACEI) each in combination with Bendroflumethiazide (thiazide diuretic) among adult hypertensive patients with ≥ grade 2 hypertension attending 3 district hospitals in Dar-es-Salaam, Tanzania. Methods:We conducted a comparative study from November 2018 to January 2019. Eligible patients received Amlodipine/Bendroflumethiazide (5/5 mg) or Lisinopril/Bendroflumethiazide (5/5 mg) drug combinations. The primary outcome measure was the BP level after 4 weeks of treatment compared to baseline BP.Results: A total of 239/266 (89.8%) patients (121 Amlodipine, 118 Lisinopril) completed the study. Their mean age was 60 ± 12 years and 69% were females. The mean ± SD baseline BP was 173 ± 19/101 ± 15 mmHg for Amlodipine and 169 ± 15/101 ± 11 mmHg for Lisinopril groups, p = 0.088. After 4 weeks of treatment, the BP dropped by a mean of 43/22 mmHg and 40/22 mmHg in the Amlodipine and Lisinopril groups, respectively (p > 0.05). Overall, after 4 weeks of treatment majority (85.4%) of study participants in the total population achieved BP control (86.0% in Amlodipine, 84.7% in Lisinopril, p = 0.792). Conclusion:Both Amlodipine and Lisinopril each in combination with Bendroflumethiazide showed impressive BP reductions in this cohort of native Tanzanian patients with ≥ stage 2 hypertension, and there was an insignificant difference between them. Both drug combinations can be used in the initial treatment plan when the priority is to reduce one's BP.