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The relationship between arterial hyperoxia exposure and clinical outcome is under increasing scrutiny. We therefore performed an update meta-analysis to evaluate the effect of arterial hyperoxia on hospital mortality in critically ill adults.We searched relevant articles for trials that investigated the relationship between arterial hyperoxia and mortality in critically ill adults. The end-point was hospital mortality of critically ill patients.Three RCTs and 26 cohort studies involving 257,223 patients were identified.Hyperoxia exposure was associated with increased mortality in critically ill patients (crude OR 1.42, 95% CI 1.26–1.61; adjusted OR 1.20, 95% CI 1.09–1.32). There was no change in significance for outcome in meta-analysis of RCTs (OR 1.36; 95% CI 1.04–1.77) and sensitivity analysis of the included prospective studies (OR 1.32; 95% CI 1.04–1.67). This association was also established in patients admitted to critical care units following cardiac arrest (adjusted OR 1.32; 95% CI 1.12–1.56), ischemic stroke (crude OR 1.31; 95% CI 1.03–1.65) and intracerebral hemorrhage (crude OR 1.47; 95% CI 1.19–1.81).The results of current meta-analysis suggest that arterial hyperoxia may be associated with increased hospital mortality in critically ill patients.Arterial hyperoxia is associated with increased hospital mortality in critically ill patients.In patients following cardiac arrest, ischemic stroke and intracerebral hemorrhage.For critically ill patients, conservative oxygen therapy may be recommended.