Background <p>Postoperative delirium is a prevalent complication following cardiac surgery. In recent studies, dexmedetomidine has been proposed as a potential alternative to mitigate this condition. This meta-analysis aimed to evaluate the efficacy and safety of dexmedetomidine for preventing postoperative delirium in cardiac surgery.</p> Methods <p>We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs), analyzing the efficacy of dexmedetomidine compared to placebo in patients undergoing cardiac surgery. We pooled risk ratios (RR) for binary outcomes with 95% confidence intervals (CI) with a random-effects model. We used R version 4.4.1 for statistical analyses. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach evaluated the quality of evidence.</p> Results <p>Our meta-analysis included 15 RCTs comprising 3675 patients, of whom 1842 (50.1%) were randomized to dexmedetomidine. The mean age ranged from 43 to 74 years among studies. Compared with placebo, dexmedetomidine significantly reduced the incidence of postoperative delirium (RR 0.67; 95% CI: 0.51 to 0.89; <i>p</i> = 0.01). There were no significant differences in hypotension (RR 1.42; 95% CI: 0.90 to 2.26; <i>p</i> = 0.13), mortality (RR 0.78; 95% CI: 0.44 to 1.36; <i>p</i> = 0.37), or acute kidney injury (RR 0.96; 95% CI: 0.61 to 1.51; <i>p</i> = 0.87) between groups. However, Trial sequential analysis showed insufficient power to discard type 1 error for our results.</p> Conclusion <p>Dexmedetomidine significantly reduced the incidence of postoperative delirium in cardiac surgery patients. Larger RCTs are warranted to validate these results.</p> Level of Evidence <p>MD.</p>