BACKGROUNDS AND STUDY AIMS: Effect of endoscopic variceal ligation (EVL) on gastric mucosal hemodynamics would differ in patients with and without large fundal varices. The aim of this study was to test this hypothesis. METHODS Twenty-seven patients with cirrhosis and large sized esophageal varices were prospectively studied. There were eight patients with large fundal varices and 19 patients without large fundal varices. Before EVL, gastric mucosal hemodynamics were endoscopically assessed by laser-Doppler velocimetry and reflectance spectrophotometry in the antrum and the corpus. In the reflectance spectrophotometric measurements, gastric mucosal hemoglobin content (IHb) and gastric mucosal oxygen saturation (ISO2) were determined. The severity of portal-hypertensive gastropathy (PHG) was also recorded at the antrum and the corpus. For data analysis, PHG was scored (absent, 0; mild, 1; severe, 2; bleeding, 3). These measurements were repeated after initial (three days after initial session) and repeated (seven days after last session) EVL. RESULTS At the antrum, neither PHG score nor gastric mucosal hemodynamic parameters were modified after initial and repeated EVL in patients with and without large fundal varices. In addition, no significant differences of the integrated changes in PHG score and gastric mucosal hemodynamic parameters were observed in the two groups. At the corpus, PHG score significantly increased after initial and repeated EVL in patients without large fundal varices. In these patients, laser-Doppler signal and ISO2 significantly decreased and IHb significantly increased after initial and repeated EVL. In contrast, PHG score, laser-Doppler signal, and ISO2 did not change significantly in patients with large fundal varices, although IHb transiently increased after initial EVL. Furthermore, the integrated changes in PHG score and gastric mucosal hemodynamic parameters were significantly lower in patients with large fundal varices than in those without. CONCLUSIONS The aggravation of PHG after EVL is due to congestion of the gastric mucosal circulation. The presence of large fundal varices plays a protective role in the development of EVL-induced gastric mucosal hemodynamic derangement.