Background/Aims Proton pump inhibitors (PPIs) are frequently prescribed to cirrhotic patients, but there is limited longitudinal evidence regarding their effects. This study aimed to assess the impact of PPIs on adverse events in cirrhotic patients. Methods A comprehensive search was conducted using the Medline and Embase databases to identify relevant articles. Pooled hazard ratios (HRs) using DerSimonian and Laird random-effects model were calculated to evaluate the risk of adverse events such as long-term mortality, hepatic decompensation, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and overall infection in cirrhotic patients with PPI use. Results The analysis included 28 studies with 260,854 cirrhotic patients. The prevalence of PPI use among cirrhotic patients was 55.93%. The use of PPIs was not significantly associated with short-term mortality in cirrhotic patients. However, long-term mortality (HR 1.321, 95% CI 1.103–1.581, P  = 0.002), decompensation (HR 1.646, 95% CI 1.477–1.835, P  < 0.001), HE (HR 1.968, 95% CI 1.372–2.822, P  < 0.001), SBP (HR 1.751, 95% CI 1.649–1.859, P  < 0.001), and infection (HR 1.370, 95% CI 1.148–1.634, P  < 0.001) were significantly associated with PPI use. Sensitivity analysis with prospective studies yielded similar results. Conclusion PPIs should be reserved for appropriate indications at lowest effective dose for cirrhotic patients due to the potential harm.