Background: Pediatric cardiac surgery is associated with a high risk of mortality and morbidity. The aim of this study was to determine if intraoperative dexmedetomidine therapy could improve survival after pediatric cardiac surgery. Methods: We conducted a retrospective review of 1384 consecutive children who underwent pediatric cardiac surgery. Amongst these, 889 received dexmedetomidine therapy and 495 did not. All children were followed for 1 year. Their in-hospital and long-term outcomes were compared by multivariate logistic regression to minimize bias, and propensity-score matched adjustment was used. Results: Children who received dexmedetomidine had lower mortality during the 30-day postoperative period compared to children who did not (1.57% vs. 4.24%; adjusted hazard ratio [HR]: 0.448; 95% confidence interval [CI]: 0.219–0.916, p = 0.028), as well as after 1 year (2.36% vs. 6.67%; adjusted [HR]: 0.487; 95% [CI]: 0.274–0.867, p = 0.014). The two groups showed no significant differences in cardiovascular complications. Conclusions: Dexmedetomidine administered intraoperatively reduced 30-day and 1-year mortality in children undergoing pediatric cardiac surgery.