The purpose of this study was to compare several diltiazem-based antihypertensive drug combinations and assess the usefulness of home blood pressure monitoring in the evaluation of the efficacy of combination pharmacotherapy. Sixteen general practitioners recruited hypertensive subjects uncontrolled on diltiazem monotherapy, who were randomized to receive eight weeks of add-on therapy with a diuretic (chlorthalidone), a dihydropyridine calcium antagonist (felodipine), an ACE inhibitor (lisinopril), or an angiotensin blocker (valsartan). Sitting office and home blood pressure was measured using electronic devices A&D 767. A total of 211 patients were randomized, and 185 completed the study. Of 52 subjects randomized to felodipine, 15 were withdrawn due to ankle edema. The additional antihypertensive effect of the second drug was smaller in 18 subjects with a white coat effect (p < 0.01). All combinations produced a significant decline in office (21.2 +/- 14.8 / 7.7 +/- 9.7 mmHg) and home (17.1 +/- 11.9 / 6.0 +/- 7.0) blood pressure (systolic / diastolic, p < 0.001). There were no differences in the efficacy of the four combinations assessed using office or home blood pressure monitoring. These data suggest that diuretics, dihydropyridines, ACE inhibitors, and angiotensin receptor blockers provide significant additional antihypertensive effects in hypertensive patients uncontrolled on diltiazem monotherapy. The diltiazem-dihydropyridine combination is often intolerable because of ankle edema. Home blood pressure monitoring is useful in the assessment of the efficacy of combination pharmacotherapy and also allows for the detection of subjects who do not require treatment intensification.