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Proton pump inhibitors (PPIs) are widely prescribed and many people remain on them for years. In some, there may be good justification for long-term use; for example, in those with oesophageal stricture, Barrett’s oesophagus or a history of a bleeding gastrointestinal ulcer, or to provide gastroprotection in those at high risk of gastrointestinal complications from taking NSAIDs. However, PPIs are often not used in line with clinical guidelines.1,2 In addition, there are concerns that many people take them for long periods to manage less serious conditions (e.g. indigestion) and may prefer taking them to addressing factors such as diet, obesity or alcohol that may be contributing to their symptoms. Although PPIs are well-tolerated, there is increasing evidence that they may be associated with a range of long-term adverse effects. Here, we review the safety of PPIs and consider whether long-term prescribing needs to be reassessed.