OBJECTIVE: The objective of this study is to compare the effects of 2 types of diuretics, indapamide and hydrochlorothiazide, added to an angiotensin-converting enzyme inhibitor, on ventricular and arterial functions in patients with hypertension and diabetes. METHODS: This is a prospective, randomized, active-controlled, PROBE design study in 56 patients (57 ± 9 years, 52% men) with mild-to-moderate hypertension and type 2 diabetes, with normal ejection fraction, randomized to either indapamide (1.5 mg Slow Release (SR)/day) or hydrochlorothiazide (25 mg/d), added to quinapril (10-40 mg/d). All patients had conventional, tissue Doppler and speckle tracking echocardiography and assessment of endothelial and arterial functions and biomarkers, at baseline and after 6 months. RESULTS: Baseline characteristics were similar between groups; systolic and diastolic blood pressures decreased similarly, by 15% and 9% on indapamide and by 17% and 10% on hydrochlorothiazide (P < .05). Mean longitudinal systolic velocity and longitudinal strain increased by 7% and 14% on indapamide (from 5.6 ± 1.8 to 6.0 ± 1.1 cm/s and from 16.2% ± 1.8% to 18.5% ± 1.1%, both P < .05), but did not change on hydrochlorothiazide (P < .05 for intergroup differences), whereas ejection fraction and radial systolic function did not change. Similarly, mean longitudinal early diastolic velocity increased by 31% on indapamide (P < .05), but did not change on hydrochlorothiazide (P < .05 for intergroup differences). These changes were associated with improved endothelial and arterial functions on indapamide, but not on hydrochlorothiazide. CONCLUSION: Indapamide was found to improve measures of endothelial and arterial functions and to increase longitudinal left ventricular function compared with hydrochlorothiazide in patients with hypertension and diabetes, after 6 months of treatment. This study suggests that indapamide, a thiazide-like diuretic, has important vascular effects that can improve ventriculoarterial coupling.