Observational studies and randomized controlled trials have yielded inconsistent findings about the association between the use of acid-suppressive drugs and the risk of pneumonia. We performed a systematic review and meta-analysis to summarize this association. We searched three electronic databases (MEDLINE PubMed, Embase and the Cochrane Library) from inception to Aug. 28, 2009. Two evaluators independently extracted data. Because of heterogeneity, we used random-effects meta-analysis to obtain pooled estimates of effect. We identified 31 studies: five case-control studies, three cohort studies and 23 randomized controlled trials. A meta-analysis of the eight observational studies showed that the overall risk of pneumonia was higher among people using proton pump inhibitors (adjusted odds ratio OR 1.27, 95% confidence interval CI 1.11-1.46, I(2) 90.5%) and histamine(2) receptor antagonists (adjusted OR 1.22, 95% CI 1.09-1.36, I(2) 0.0%). In the randomized controlled trials, use of histamine(2) receptor antagonists was associated with an elevated risk of hospital-acquired pneumonia (relative risk 1.22, 95% CI 1.01-1.48, I(2) 30.6%). Use of a proton pump inhibitor or histamine(2) receptor antagonist may be associated with an increased risk of both community- and hospital-acquired pneumonia. Given these potential adverse effects, clinicians should use caution in prescribing acid-suppressive drugs for patients at risk.