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To assist clinicians in counseling patients regarding the risk of adverse events from proton pump inhibitors (PPIs), by synthesizing evidence from published systematic reviews of antireflux therapy.Cochrane Library, CINAHL, PubMed, Web of Knowledge.Overview based on PRISMA reporting standards (preferred reporting items for systematic reviews and meta-analyses) of English-language meta-analyses and systematic reviews of PPI therapy for reflux disease through December 2014. Two independent investigators assessed study eligibility, rated the review quality with AMSTAR criteria (assessing the methodological quality of systematic reviews), and abstracted data for adverse events.Thirty-three systematic reviews met inclusion criteria. The most commonly reported adverse events were community-acquired pneumonia (odds ratios, 1.04-1.92), with a greater association noted with shorter duration of therapy and higher doses. Hip fractures were also associated with PPI use (odds ratios, 1.16-1.50), especially with long-term therapy. Last, enteric infection with Clostridium difficile was more common with PPI therapy (odds ratios, 1.69-1.33). Other less commonly reported adverse events included electrolyte and vitamin deficiency. Risk factors for adverse events are reported in the text.Our overview shows that PPI therapy is associated with significant and potentially serious adverse events that should be discussed with patients. The effect sizes and risk factors provided should facilitate this discussion and promote shared decision making.