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Aim: To determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders., Methods: One hundred and two consecutive patients of cirrhosis of liver with significant portal hypertension were included. Hepatic venous pressure gradient (HVPG) was measured at the base line and after proper optimization of dose; chronic response was assessed at 3 mo. Carvedilol non-responders were given simvastatin 20 mg per day (increased to 40 mg per day at day 15). Carvedilol plus simvastatin was continued for 1 mo and hemodynamic response was again measured at 1 mo., Results: A total of 102 patients with mean age of 58.3 ± 6.6 years were included. Mean baseline HVPG was 16.75 ± 2.12 mmHg and after optimization of dose and reassessment of HVPG at 3 mo, mean reduction of HVPG from baseline was 5.5 ± 1.7 mmHg and 2.8 ± 1.6 mmHg among responders and non-responders respectively ( P < 0.001). Addition of simvastatin to carvedilol non-responders resulted in significant response in 16 patients (42.1%) and thus overall response with carvedilol and carvedilol plus simvastatin was seen in 78 patients (80%). Two patients were removed in chronic protocol study with carvedilol and three patients were removed in carvedilol plus simvastatin study due to side effects., Conclusion: Addition of simvastatin to carvedilol non-responders may prove to be an excellent rescue therapy in patients with portal hypertension., Competing Interests: Conflict-of-interest statement: The Authors have no conflict of interest.