The etiology of inflammation of the gastric cardia (carditis) is controversial, and gastroesophageal reflux disease (GERD) and H. pylori infection have been proposed as etiological factors. This study aimed to investigate the effect of acid suppression on histological changes in the gastric cardia. Gastric cardia biopsies of reflux patients were evaluated at baseline and after proton pump inhibitor (PPI) therapy. The updated Sydney classification was used to score the biopsies, and carditis scores (pre- and post-PPI therapy) were compared. A total of 31 patients were included, of which 5 patients were excluded, as cardiac mucosa was not documented in either pre- or post-PPI biopsies. The mean duration of PPI therapy was 30 months (SE, 3.04 months). There was no significant change in carditis scores post-PPI therapy. The mean mononuclear and neutrophil scores were 1.23 and 0.35 pre-PPI therapy and 1.73 and 0.62 post-PPI therapy, respectively. No change in mean intestinal metaplasia and atrophy scores was identified. In conclusion, acid suppressive therapy with PPI did not lead to a significant reduction in carditis scores. These results suggest that GERD probably does not play a major role in the pathogenesis of inflammation in the gastric cardia.