INTRODUCTION AND OBJECTIVES: The potential benefits of branched-chain amino acids (BCAAs) in cirrhosis extend beyond just the improvement of nutritional status. Their effects include improvement of glucose tolerance, oxidative stress, and inflammatory markers, as has been shown in several studies. A dual nutritional approach of a high-protein, high-fiber diet plus BCAAs in cirrhosis could have additional benefits, compared with BCAAs alone. Such an approach has not been explored and therefore the aim of the present study was to evaluate the effect of a combination of a high-protein, high-fiber diet plus BCAA supplementation over a 6-month period of time on the nutritional status of patients with cirrhosis, as well as its safety and tolerability for those same patients. METHODS: An open, randomized clinical trial was conducted. Patients were randomized to one of two groups: the BCAAs+HPHF diet intervention group: a high-protein, high-fiber diet with 1.2g/kg protein and 30g of fiber plus supplementation with oral branched-chain amino acids 110g daily and the HPHF diet control group: a high-protein, high-fiber diet with 1.2g/kg protein and 30g of fiber. The differences between the treatment groups were compared using the unpaired T test and the differences at the end of treatment were compared using the paired T test. RESULTS: A total of 72 patients were included, 37 in the intervention group and 35 in the control group. At the end of the study period, ammonia and glucose levels showed no significant increase in either group, reflecting the safety of the BCAA supplement. Furthermore, muscle and fat mass were evaluated through triceps skinfold thickness and mid-arm muscle circumference measurements. There was an increase in muscle mass and a decrease in fat mass in the BCAA group, but not in the control group. After the intervention, there were no significant changes in the Psychometric Hepatic Encephalopathy Score or the Critical Flicker Frequency score results in either group, and no episodes of hepatic encephalopathy were observed during the treatment period. CONCLUSION: Supplementation with branched-chain amino acids plus a high-fiber, high-protein diet is a safe intervention in patients with cirrhosis. It helps increase muscle mass and does not raise the levels of ammonia or glucose, nor is it associated with the development of hepatic encephalopathy.