Background: Only 40% to 60% of patients with essential hypertension respond adequately to antihypertensive monotherapy. The combination of an angiotensin-converting enzyme inhibitor and a calcium antagonist, both of which have tissue-protective properties but different mechanisms of action, may lead to an additive antihypertensive effect. Objective: The aim of this study was to evaluate the effects of a fixed, low-dose combination of verapamil sustained-release (SR) and trandolapril in patients with mild to severe essential hypertension uncontrolled by monotherapy. Methods: A total of 168 patients aged 18 to 70 years with mild to severe hypertension (systolic blood pressure [SBP] 140–200 mm Hg and diastolic blood pressure [DBP] 90–119 mm Hg) were enrolled in the study. After a 1-week placebo run-in period, all patients received a fixed combination of verapamil SR 180 mg and trandolapril 2 mg once a day for 6 weeks. Blood pressure was measured before and after the placebo run-in period and at weeks 1, 3, and 6 of the active-treatment period. Results: A total of 138 patients (77 women and 61 men; mean age 51.6 ± 10.3 years, range 21–70 years) completed the study. Sitting SBP/DBP values were significantly reduced from 169.6 ± 16.6/101.7 ± 8.0 mm Hg at the end of the placebo run-in period (week 0) to 137.6 ± 13.1/85.2 ± 8.0 mm Hg after 6 weeks of treatment ( P < 0.001 vs week 0 values for SBP and DBP). The percentage reductions in SBP and DBP were 19% and 17%, respectively. The target blood pressure (<140/90 mm Hg and reduction in DBP of > 10 mm Hg) was achieved in 70% of the patients at the end of 6 weeks' treatment. Heart rate was reduced slightly, but significantly ( P < 0.001). The left ventricular mass index detected by echocardiography was significantly reduced from 124.0 ± 32.1 g/m 2 to 118.2 ± 25.9 g/m 2 ( P < 0.01), and the E/A ratio of mitral inflow increased significantly from 0.9 ± 0.4 to 1.0 ± 0.4 ( P < 0.01). Adverse effects were reported in 17 of 138 patients (12%) (cough, 3; headache, 5; palpitation, 2; constipation, 3; tinnitus, 2; edema, 1; flushing, 1); 2 patients were withdrawn from the study because of side effects (1 with severe flushing and 1 with cough). No clinically relevant changes in laboratory parameters (glucose, urea, creatinine, uric acid, electrolytes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, high-density lipoprotein cholesterol, very low density lipoprotein cholesterol, triglycerides, and protein) were detected. Conclusions: Based on the results of the study, the fixed combination of verapamil SR 180 mg and trandolapril 2 mg has good efficacy and tolerability, little impact on metabolic parameters, and a regressive effect on left ventricular hypertrophy in patients with mild to severe hypertension.