Salvo EM, Ferko EC, Cash SB, et al. - This study was carried out to assess an umbrella review to comprehensively assess associations between adverse events and proton pump inhibitor (PPI) use Researchers carried out searches of PubMed and EMBASE from 2015 to July 2019. Quality and certainty of evidence were evaluated by using AMSTAR 2 and GRADE. They enrolled 42 systematic reviews with meta-analyses, supported predominantly by observational evidence. This review distinguished several published relationships between PPIs and adverse outcomes, nevertheless, there is a need for further evaluation to understand their clinical significance and the likelihood of causal relationship. It may be necessary for clinicians to consider alternative treatment strategies, especially when PPI efficacy is suboptimal whether higher quality evidence is generated substantiating the potential risks.