Background: Attenuating aldosterone (ALDO) effects may be important in slowing kidney and cardiovascular disease progression. This study tested whether ACE inhibitor (I) therapy achieves lower plasma (p) ALDO levels than angiotensin receptor blocker (ARB) therapy when they are used under usual clinical conditions in chronic kidney disease (CKD) patients. Methods: Consecutive CKD patients (n = 123) were studied. They were clinically stable and receiving either ACEI (n = 77) or ARB (n = 46) (physician’s choice) for ≧3 months. Results: Mean pALDO in the ACEI cohort was 7.8 ± 5.7 (SD) ng/dl compared to 12.3 ± 9.8 ng/dl in the ARB cohort (p = 0.0018, normal ambulatory pALDO 9.4–33.8 ng/dl). The pALDO difference was not explained by differences in age, sex, race, body weight, diagnosis of diabetes; the use of β-blockers, calcium channel blockers or diuretic; systolic or diastolic blood pressure; plasma renin, serum creatinine, sodium, potassium, or bicarbonate levels; 24-hour urine potassium, sodium, urea or protein excretion; or ACEI or ARB dose. Conclusions: Mean pALDO is about 60% higher with ARB therapy than ACEI therapy when these drugs are customarily used in CKD patients. This difference could be clinically important with regard to kidney and cardiovascular protection.