Endoscopic variceal ligation is an effective therapy for variceal bleeding, and use of the method has recently been increasing. We evaluated the clinical usefulness of prophylactic endoscopic variceal ligation. Twenty-two patients with enlarged, tortuous varices and "red color signs" were selected. These patients were treated with ligation therapy alone and the varices were eradicated, i.e., reduced to small, straight varices without red color signs. Ligation therapy was withdrawn if the general condition of the patient worsened or if the varices could not be removed by suction. Follow-up endoscopy was performed every 4 months, and another ligation was performed if there were recurrent varices or variceal bleeding. The total reduction rate was 86.4%, and eradication required two sessions of therapy and 30 days of hospitalization on average. Complications included esophageal injury in 1 patient and treatment-induced bleeding in 1 patient; both complications were easily controlled. No variceal bleeding occurred after the eradication. There was no mortality due to gastrointestinal bleeding during the median follow-up period of 346 days. Prophylactic endoscopic variceal ligation made it possible to prevent fatal variceal bleeding with a minimum risk of complications, suggesting that this could be an alternative method for the prevention of first-time variceal bleeding.