Variceal bleeding is a consequence of portal hypertension, which in turn is the major complication of hepatic cirrhosis. Given the high rate of mortality of the first bleeding episode, primary prophylaxis to prevent bleeding from varices and portal hypertensive gastropathy is the current optimal therapeutic approach. The difficulty in identification of patients with varices who will bleed, before they do so, can justify a strategy of treating all patients with varices prophylactically. We evaluated the various therapies that have been assessed in randomized controlled trials for prevention of first bleeding, using meta-analysis where applicable. The current first choice treatment is non-selective beta-blockers; it is cheap, easy to administer, and is effective in preventing the first variceal haemorrhage and bleeding from gastric mucosa. Combination drug therapy of beta-blockers and nitrates looks promising, but needs further evaluation in randomized controlled trials. The conflicting results of the randomized studies of endoscopic banding ligation and the small number of patients and clinical events, as well as the cost, do not warrant any change in current practice. However, endoscopic banding ligation may be a reasonable alternative for patients who cannot tolerate, or have contraindications to beta-blockers or no haemodynamic response to the drug therapy, but this must be proved in randomized trials.