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Purpose: Proton pump inhibitors (PPIs), one of the most widely used medications, are commonly used to suppress several acid-related upper gastrointestinal disorders. Acid-suppressing medication use could be associated with increased risk of community-acquired pneumonia (CAP), although the results of clinical studies have been conflicting., Data Sources: A comprehensive search of MEDLINE, EMBASE and Cochrane library and Database of Systematic Reviews from the earliest available online year of indexing up to October 2018., Study Selection: We performed a systematic review and meta-analysis of observational studies to evaluate the risk of PPI use on CAP outcomes., Data Extraction: Included study location, design, population, the prevalence of CAP, comparison group and other confounders. We calculated pooled odds ratio (OR) using a random-effects meta-analysis., Results of Data Synthesis: Of the 2577 studies screening, 11 papers were included in the systematic review and 7 studies with 65 590 CAP cases were included in the random-effects meta-analysis. In current PPI users, pooled OR for CAP was 1.86 (95% confidence interval (CI), 1.30-2.66), and in the case of recent users, OR for CAP was 1.66 (95% CI, 1.22-2.25). In the subgroup analysis of CAP, significance association is also observed in both high-dose and low-dose PPI therapy. When stratified by duration of exposure, 3-6 months PPIs users group was associated with increased risk of developing CAP (OR, 2.05; 95% CI, 1.22-3.45). There was a statistically significant association between the PPI users and the rate of hospitalization (OR, 2.59; 95% CI, 1.83-3.66)., Conclusion: We found possible evidence linking PPI use to an increased risk of CAP. More randomized controlled studies are warranted to clarify an understanding of the association between PPI use and risk of CAP because observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding., (© The Author(s) 2020. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)