BACKGROUND: Many patients are diagnosed with hypertension each year, making rapid and effective control of blood pressure (BP) crucial. Appropriate first-line treatment is important, and special attention should be paid to the positive effects of lowering BP early. Perindopril 3.5 mg/amlodipine 2.5 mg (P3.5/A2.5) is a single-pill combination suitable for first-line use. The doses of each component of the single-pill combination were selected for a first-line setting. OBJECTIVE: To investigate the effectiveness of the P3.5/A2.5 combination at lowering BP compared with renin-angiotensin system (RAS)-inhibitor monotherapies, after 1 month of treatment. METHODS: Individual patient data from three randomized controlled trials were used to evaluate the efficacy of P3.5/A2.5 versus RAS-inhibitor monotherapies after 1 month in 5496 patients with hypertension, in a combined analysis. RESULTS: P3.5/A2.5 was well tolerated and significantly more effective at reducing BP after 1 month than RAS-inhibitor monotherapies (perindopril 5 mg, irbesartan 150 mg or valsartan 80 mg). P3.5/A2.5 was associated with a significantly lower SBP (P = 0.002) and DBP (P = 0.005) after 1 month of treatment compared with RAS-inhibitor monotherapies. CONCLUSION: In a large patient population, early administration of P3.5/A2.5 resulted in a significantly greater BP-lowering effect than perindopril, irbesartan or valsartan monotherapies after 1 month. Reducing BP levels within a month of treatment may reasonably be expected to lead to a reduced risk of cardiovascular events.