A new study published the Canadian Journal of Gastroenterology & Hepatology investigated whether primary prophylaxis in cirrhotic patients with variceal bleeding with lactulose or L-ornithine L-aspartate or rifaximin, is better than placebo for avoiding the development of hepatic encephalopathy. This was a randomized, double-blinded, placebo-controlled clinical trial including cirrhotic patients with variceal bleeding without minimal or clinical hepatic encephalopathy at admission. Here, 87 patients were randomized either of the four groups - lactulose, L-ornithine L-aspartate, rifaximin or placebo. It was observed that the basal characteristics were comparable between the groups. Relative to placebo, the frequency of development of hepatic encephalopathy was as follows: lactulose - 54.5% versus 27.3%; L-ornithine L-aspartate - 54.5% versus 22.7%; and rifaximin - 54.5% versus 23.8%. On the other hand, no significant difference was noted between the three groups receiving anti-ammonium drug. Furthermore, among those receiving lactulose, 59.1% had diarrhea while 45.5% had abdominal discomfort, bloating, and flatulence. Whereas, two patients (10%) treated with lactulose and a patient (4.5%) in the placebo group developed spontaneous bacterial peritonitis due to E. coli. One of these patients died due to recurrent variceal bleeding. No other adverse effects could be associated with the use of these drugs. From the results, it was inferred that anti-ammonium drugs, particularly L-ornithine L-aspartate and rifaximin, are effective in preventing the development of hepatic encephalopathy in cirrhotic patients with variceal bleeding.