OBJECTIVE Endoscopic injection sclerotherapy (EIS) has been extensively applied world wide. There are few reports, however, addressing the long-term prognosis (>20 years), although more than two decades have elapsed since the introduction of EIS for esophageal varices. Therefore, the cases of EIS performed in the past 25 years were reviewed to evaluate the long-term results of this procedure. METHODS There were 602 patients who underwent EIS for esophageal varices between 1981 and 2005, involving a total of 1,964 applications of this procedure. The procedure begins by intravascular injection of 10-20 mL of 5% ethanolamine oleate. The long-term follow-up data were evaluated with primary reference to changes in esophageal varices, survival rate, bleeding rate, causes of death and re-bleeding. RESULTS In 188 patients with known final endoscopic findings, the gross morphologic status was F1 in 65 patients (34.6%) and F0 in 123 patients (65.4%), only 22 patients (11.7%) were positive for red color sign. The survival rate was 47.4% at 5 years, 25.9% at 10 years, and 13.9% at 15 years. Rebleeding occurred in 93 patients (15.4%). The bleeding rate was 22.9% at 5 years, 28.9% at 10 years, and 28.9% at 15 years. The causes of death were hepatic failure in 244 patients and hepatic cancer in 88 patients, 19 patients died as a result of bleeding from varices (4.8%), 3 patients who died due to therapeutic procedure of EIS. CONCLUSIONS Both the survival rate and rebleeding rate associated with EIS were comparable to those undergoing surgical treatment in patients whose clinical characteristics were matched. EIS is a minimally invasive treatment method that is considered to be an effective first-line treatment for esophageal varices.