The extent to which chronic kidney disease (CKD) affects achievement of blood pressure targets is not comprehensively understood. We evaluated the effects of CKD (estimated glomerular filtration rate: <60 mL/min per 1.73 m(2)) on achievement of blood pressure control (nondiabetic: <140/90 mm Hg; diabetic: <130/85 mm Hg) using data from the Guidelines for Drug Therapy of Hypertension Trial. This 15-month study obtained outpatient blood pressures from 3 Veteran's Affairs institutions. Among 9985 subjects with hypertension, we evaluated the association of CKD with achieved control and antihypertensive medication use. We also explored the association between the number of antihypertensives and systolic, diastolic, and pulse pressure. After 15 months, 41% of participants met blood pressure targets. CKD was not associated with control (adjusted odds ratio: 1.04; 95% CI: 0.93 to 1.15). However, CKD was associated with higher odds of use of >or=3 medications among nondiabetic subjects (odds ratio: 1.46; 95% CI: 1.25 to 1.71) and diabetic subjects (odds ratio: 1.40; 95% CI: 1.17 to 1.66). A significant interaction was observed between CKD and the number of antihypertensives as determinants of diastolic and pulse pressures. Among non-CKD participants, a greater number of antihypertensives (0 compared with 4) was associated with wider pulse pressure (Delta5.2 mm Hg; P<0.001), mainly because of higher systolic pressures (Delta3.6 mm Hg; P=0.001). Among participants with CKD, although greater numbers of antihypertensives were associated with even wider pulse pressures (Delta8.3 mm Hg; P<0.001), this was primarily because of lower diastolic pressures (Delta4.8 mm Hg; P<0.01). Among participants with CKD, greater use of antihypertensives was associated with lower diastolic pressures. Given recent evidence suggesting adverse effects of diastolic hypotension, these results suggest potential risks in patients with CKD from aggressive attempts to control systolic blood pressure.