OBJECTIVE To determine the frequency of Helicobacter pylori (H. pylori) infection in glaucoma patients and in anemic control participants. METHODS Prospective, nonrandomized, comparative study. METHODS The authors investigated 32 patients with chronic open-angle glaucoma (COAG), 9 patients with pseudoexfoliation glaucoma (PEG), and 30 age-matched anemic control participants. METHODS Upper gastrointestinal endoscopy was performed to evaluate macroscopic abnormalities, and gastric mucosal biopsy specimens were obtained for the presence of H. pylori infection tested by rapid urease slide test (CLO test) and by Cresyl fast violet staining, Giemsa staining, or both. The presence of gastritis was classified in accordance with the Sydney system by using hematoxylin and eosin stain. In addition, intestinal metaplasia was evaluated with Alcian blue stain. Saliva samples were also tested by CLO. Serum was analyzed for the presence of H. pylori-specific IgG antibodies by enzyme-linked immunosorbent assay. METHODS Histologic examination for the presence of H. pylori. RESULTS In 87.5% of the COAG patients, 88.9% of the PEG patients, and 46.7% of the anemic control participants, H. pylori infection was histologically confirmed (odds ratio, 8.00; chi-square, 11.81; P = 0.0006 and 9.14; chi-square, 5.01; P = 0.02, respectively). H. pylori was detected by urease test: (1) in the gastric mucosa in 71.9% of the COAG patients, in 77.8% of the PEG patients, and in 46.7% of the anemic control participants (P = 0.03 and P > 0.05, respectively); and (2) in the saliva in 37.5% of the COAG patients, in 55.6% of the PEG patients, and in 30% of the anemic control participants (P > 0.05). Sixty-eight percent of glaucoma patients and 30% of anemic control participants were seropositive for H. pylori (P = 0.002). When compared with anemic control participants, glaucoma patients exhibited less often endoscopic normal appearance of gastric mucosa (P = 0.01), and more often antral gastritis (P = 0.0004) or peptic ulcer disease (P = 0.01). Histologic grade 3 gastritis was observed only in the glaucoma patients (P = 0.03). CONCLUSIONS H. pylori infection seems more frequent in glaucoma patients. If confirmed, this may indicate either a common factor that causes susceptibilities to both glaucoma and H. pylori infection or that H. pylori may be a causal factor for developing glaucoma.