The authors tested the hypothesis that an aggressive antihypertensive treatment is beneficial in protecting against target organ damage (TOD) in patients with type 2 diabetes/prediabetes. The authors enrolled 60 patients with uncontrolled hypertension and diabetes/prediabetes and performed clinic, home, and ambulatory blood pressure (BP) monitoring. Irbesartan, amlodipine, and indapamide were used according to a titration schedule from step 1 to 5 for target home BP level ≤125/75mmHg. The flow-mediated vasodilation (FMD), radial augmentation index (AI), pulse wave velocity (PWV), and urinary albumin excretion ratio (UACR), as a surrogate marker of TOD, were measured at baseline and 6 months. Compared with baseline, clinic, home, and ambulatory BP measures were significantly lower in the sixth month. FMD was increased significantly and AI, PWV, and UACR were reduced by the treatment. The extent of the changes in PWV and UACR were associated with the changes in all BP measures, but only the change in home morning BP was associated with the change in FMD. The change in AI was not associated with the change in BP levels, but was associated with the change in PWV. A very aggressive antihypertensive therapy guided by home morning BP was effective for surrogate end points in patients with diabetes/prediabetes.