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The influence of dexmedetomidine on postoperative delirium (POD) in adult surgical patients remains controversial. We aimed to analyse whether dexmedetomidine use could decrease POD incidence in this population and its relation to timing of dexmedetomidine administration and patient age.We used random-effects modelled meta-analysis, trial sequential analysis, and followed Cochrane methodology with Grading of Recommendations Assessment, Development, and Evaluation (GRADE). PubMed and Cochrane library were searched up to July 2017 for randomised controlled trials that analysed POD incidence of adult surgical patients (age ≥18 yr) after dexmedetomidine administration.Eighteen studies (comprising 3309 patients) were included. There was decreased risk of POD with dexmedetomidine use for the entire adult surgical population [odds ratio (OR) 0.35; 95% confidence interval (CI) 0.24–0.51)], with firm evidence from trial sequential analysis. Pre-specified subgroup analyses confirmed this result with firm evidence for cardiac and non-cardiac surgical patients, (OR 0.41; 95% CI 0.26–0.63) and (OR 0.33; 95% CI 0.18–0.59), respectively. We also found firm evidence for reduction of POD if dexmedetomidine is administered during the postoperative period (OR 0.30; 95% CI 0.21–0.44), in patients aged <65 yr (OR 0.19; 95% CI 0.10–0.36) or ≥65 yr (OR 0.44; 95% CI 0.30–0.65). Evidence for dexmedetomidine's influence on secondary outcomes (in-hospital mortality, intensive care unit and hospital length of stay, bradycardia, and hypotension) is thus far insufficient to draw conclusions.Dexmedetomidine can reduce POD incidence for adult cardiac and non-cardiac surgical patients. The optimal dose and timing of dexmedetomidine and influence on other outcomes or particular patient populations with risk factors warrants further studies.PROSPERO: CRD42017072380.