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Background: Opioid-based anesthesia (OBA) has traditionally been the standard approach for intraoperative analgesia, but its use is associated with adverse effects such as respiratory depression, nausea and vomiting, hyperalgesia, and delayed recovery. To mitigate these issues, opioid-free anesthesia (OFA) regimens combining non-opioid agents (e.g., dexmedetomidine, ketamine, lidocaine, magnesium, esmolol) have been increasingly adopted. Although several randomized controlled trials (RCTs) have compared OFA with OBA in laparoscopic surgery, results remain heterogeneous.Methods: We performed a systematic review and meta-analysis of RCTs enrolling adult patients undergoing elective laparoscopic procedures, randomized to receive either OFA or OBA. Primary outcomes were postoperative pain intensity and incidence of postoperative nausea and vomiting (PONV). Secondary outcomes included intraoperative and postoperative opioid consumption, hemodynamic stability, quality of recovery, and length of hospital stay. Risk of bias was assessed with the Cochrane RoB 2.0 tool, and certainty of evidence was graded using GRADE methodology.Results: Sixteen RCTs, comprising over 1,300 patients undergoing laparoscopic cholecystectomy, gynecologic laparoscopy, bariatric surgery, colectomy, and urologic procedures, were included. Compared with OBA, OFA protocols consistently reduced postoperative opioid requirements and were associated with a lower incidence of PONV in several trials. Postoperative pain scores within 24 h were generally similar or modestly improved with OFA. Hemodynamic adverse events, including bradycardia and hypotension, occurred more frequently with dexmedetomidine-based regimens. Some studies reported slightly prolonged emergence or recovery times, but length of hospital stay was unaffected.Conclusions: OFA is a safe and feasible alternative to OBA in laparoscopic surgery and may offer advantages in reducing opioid consumption and PONV. However, considerable heterogeneity in drug protocols, study designs, and reported outcomes limits the ability to draw definitive conclusions. Large multicenter RCTs with standardized OFA strategies are needed to clarify its role in enhanced recovery pathways.