Gastric infection by H. pylori is the most common cause of ulcer disease and gastric cancer. The mechanism of progression from gastritis and inflammation to, in a fraction of those infected, ulcers and cancer, is not definitively known. Significant acidity is unique to the gastric environment and is required for ulcer development. The interplay between gastric acidity and H. pylori pathogenesis is important in progression to advanced disease. The aim of this study was to characterize the impact of acid on gastric epithelial integrity and cytokine release and how H. pylori infection alters these responses. HGE-20 cells were grown on porous inserts, and survival, barrier function, and cytokine release were studied at various apical pHs in the presence and absence of H. pylori. With apical acidity, gastric epithelial cells demonstrate increased barrier function, as evidenced by increased transepithelial electrical resistance (TEER) and decreased paracellular permeability. This effect is reduced in the presence of wildtype, but not urease knockout H. pylori. Epithelial inflammatory response is also modulated by both acidity and H. pylori infection. Without H. pylori, epithelial IL-8 release decreases in acid while IL-6 release increases. In the presence of H. pylori, acidic pH diminishes the magnitude of the previously reported increase in IL-8 and IL-6 release. H. pylori interferes with the gastric epithelial response to acid, contributing to altered barrier function and inflammatory response. H. pylori diminishes acid-induced tightening of cell junctions in a urease dependent manner, suggesting local pH elevation promotes barrier compromise and progression to mucosal damage.