Context Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. Objective To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a β-blocker (metoprolol) on hypertensive renal disease progression. Design, Setting, and Participants Interim analysis of a randomized, doubleblind, 3 × 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m2) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. Interventions Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n=217), ramipril, 2.5 to 10 mg/d (n=436), or metoprolol, 50 to 200 mg/d (n=441), with other agents added to achieve 1 of 2 blood pressure goals. Main Outcome Measures The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m2end-stage renal disease, or death. Results Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m2/y) slower mean decline in GFR over 3 years (P=.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [Cl], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P=.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95 % Cl, 13 %-56%), a 36% slower mean decline in GFR after 3 months (P=.002), and less proteinuria (P<.001). Conclusion Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria. © 2001 American Medical Association.