Objectives: To evaluate the effects of manidipine versus amlodipine on blood pressure, albuminuria, insulin sensitivity, adiponectin, TNF-α and C-reactive protein in nondiabetic subjects with metabolic syndrome (ATP-III definition), including impaired fasting glucose (>5.6 mmol/l) and hypertension. Methods: In total, 64 patients were recruited and randomly assigned to manidipine 20 mg versus amlodipine 10 mg (for 12 ± 2 weeks). Results: Blood pressure was reduced to a similar extent (p < 0.001) by both treatments. Albuminuria was significantly reduced by manidipine (-37.3%; p = 0.003), but not by amlodipine. C-reactive protein was reduced similarly (p < 0.01) by both treatments. Plasma adiponectin was increased (32.9%; p = 0.011) and plasma TNF-α was reduced by manidipine (-37.1%; p = 0.019), but neither was significantly changed by amlodipine. The HOMA insulin resistance index was significantly reduced by manidipine (-21.3%; p = 0.007), but not by amlodipine (-8.3%; p = 0.062). Tolerability with manidipine was superior to that with amlodipine (p = 0.04). Conclusion: These data support the added value of manidipine in renal and metabolic protection beyond blood pressure reduction in the treatment of hypertensive patients with metabolic syndrome.