The purpose of this study was to assess the factors affecting the efficacy of combination therapy with losartan and thiazide, with a focus on the significance of salt excretion, via a multicenter observational study. Adult patients with essential hypertension showing therapy resistance to angiotensin receptor blocker (ARB) as a monotherapy or in combination with Ca channel blockers (CCB) were enrolled, and their previously administered ARBs were replaced with the combination tablet containing losartan (50 mg per day) and hydrochlorothiazide (12.5 mg per day). Blood pressure and biochemical parameters were monitored for a year. The baseline blood pressure (153.4±14.8/86.4±11.3 mm Hg) was significantly lowered at the 3rd month (137.3±17.4/78.2±11.1 mm Hg, n=93) and was maintained at this lower level until the 12th month (135.3±14.0/76.4±11.1 mm Hg, n=74). The baseline value of estimated salt excretion (eSE), calculated using Tanaka's formula, differed significantly between the high and low treatment response groups, which were defined by the average change in mean blood pressure (MBP-C, -11.3 mm Hg; eSE=10.8±2.9 g per day in high responders vs. 9.2±2.3 g per day in low responders, P=0.004). Univariate and multivariate analyses showed a significant correlation between eSE and MBP-C (R=-0.288, P=0.007) and indicated the clinical effectiveness of eSE as a possible predictor for MBP-C (P=0.021). In addition, the urine Na-to-Cr ratio (NCR) demonstrated significant correlations with eSE (R=0.848, P<0.001) and MBP-C (R=-0.344, P<0.001). These results suggest that eSE or NCR could, to a certain extent, predict the efficacy of combination therapy with losartan and low-dose thiazide in patients demonstrating ARB resistance. Combination therapy with losartan and thiazide might thus be suitable for patients with a large amount of salt excretion.