Reduction of gastric acid secretion by acid-suppressive therapy allows pathogen colonization from the upper gastrointestinal tract. The bacteria and viruses in the contaminated stomach have been identified as species from the oral cavity. To examine the association between the use of acid-suppressive drugs and occurrence of community-acquired pneumonia. Incident acid-suppressive drug users with at least 1 year of valid database history were identified from the Integrated Primary Care Information database between January 1, 1995, and December 31, 2002. Incidence rates for pneumonia were calculated for unexposed and exposed individuals. To reduce confounding by indication, a case-control analysis was conducted nested in a cohort of incident users of acid-suppressive drugs. Cases were all individuals with incident pneumonia during or after stopping use of acid-suppressive drugs. Up to 10 controls were matched to each case for practice, year of birth, sex, and index date. Conditional logistic regression was used to compare the risk of community-acquired pneumonia between use of proton pump inhibitors (PPIs) and H2-receptor antagonists. Community-acquired pneumonia defined as certain (proven by radiography or sputum culture) or probable (clinical symptoms consistent with pneumonia). The study population comprised 364,683 individuals who developed 5551 first occurrences of pneumonia during follow-up. The incidence rates of pneumonia in non-acid-suppressive drug users and acid-suppressive drug users were 0.6 and 2.45 per 100 person-years, respectively. The adjusted relative risk for pneumonia among persons currently using PPIs compared with those who stopped using PPIs was 1.89 (95% confidence interval, 1.36-2.62). Current users of H2-receptor antagonists had a 1.63-fold increased risk of pneumonia (95% confidence interval, 1.07-2.48) compared with those who stopped use. For current PPI users, a significant positive dose-response relationship was observed. For H2-receptor antagonist users, the variation in dose was restricted. Current use of gastric acid-suppressive therapy was associated with an increased risk of community-acquired pneumonia.