Background: Intraoperative infusion of remifentanil is widely used for analgesia; however, remifentanil administration has been associated with hyperalgesia, respiratory depression, nausea and vomiting, emergence agitation, and delirium. Intraoperative infusion of dexmedetomidine may be an effective alternative for pain control. Method: We conducted a comprehensive literature review of the PubMed, Embase, and Cochrane Library databases for relevant randomized controlled trials (RCTs) comparing intraoperative infusion of dexmedetomidine and remifentanil. Outcome measures included: requirement for rescue analgesia, evaluation of postoperative analgesia by pain scores, intraoperative and postoperative blood pressure and heart rate, and incidence of postoperative vomiting and shivering. Results: Twelve RCTs were included in the meta-analysis. Results demonstrated significant decreases in the requirement for rescue analgesia (OR: 0.42, 95% CI: 0.22, 0.80, P = 0.008, I-2 = 0%), postoperative pain score (mean difference (MD): -1.60, 95% CI: -2.24, -0.96, P < 0.00001, I-2 = 62%), and incidence of postoperative vomiting (OR: 0.42, 95% CI: 0.21, 0.85, P = 0.02, I-2 = 14%) in patients administered intraoperative dexmedetomidine versus remifentanil. There were no differences in incidence of intraoperative and postoperative hypotension (odds ratio (OR): 0.72, 95% confidence interval (CI): 0.24, 2.17, P = 0.56, I-2 = 72%), incidence of intraoperative and postoperative bradycardia (OR: 1.06, 95% CI: 0.48, 2.34, P = 0.89, I-2 = 63%), or incidence of postoperative shivering (OR: 0.61, 95% CI: 0.29, 1.30, P = 0.20, I-2 = 24%). Conclusions: Intraoperative infusion of dexmedetomidine can alleviate postoperative pain in patients undergoing general anesthesia compared to remifentanil.