Abstract Introduction and objectives Multimodal Analgesia (MMA) has shown promising results in postoperative outcomes across a broad spectrum of surgeries, including bariatric surgery. We compared the analgesic effect immediately after Laparoscopic Bariatric Surgery (LBS) of the combined effect of MMA and methadone against two techniques that were based mainly on the use of high-potency medium-acting opioids. Methods Two hundred seventy-one patients were retrospectively reviewed. The primary outcome was postoperative pain score > 3/10 measured by the Verbal Numeric Scale (VNS) during the Postanesthetic Care Unit (PACU) stay. The three protocols of intraoperative analgesia were: (P1) sufentanil at anesthetic induction followed by remifentanil infusion; (P2) sufentanil at induction followed by dexmedetomidine infusion; and (P3) remifentanil at induction followed by MMA including dexmedetomidine, magnesium, lidocaine, and methadone. Only P1 and P2 patients received morphine toward the end of surgery. Poisson regression was used to adjust confounding factors and calculate Prevalence Ratio (PR). Results Postoperative VNS > 3 was recorded in 135 (49.81%) patients, of which 93 (68.89%) were subjected to P1, 25 (18.56%) to P2, and 17 (12.59%) to P3. In the final adjusted model, both anesthetic techniques (P3) (PR = 0.10; 95% CI [0.03-0.28]), and (P2) (PR = 0.42%; 95% CI [0.20-0.90]) were associated with lower occurrence of VNS > 3, whereas age range 20-29 was associated to higher occurrence of VNS > 3 (PR = 3.21; 95% CI [1.22-8.44]) in PACU. Postoperative Nausea and Vomiting (PONV) was distributed as follows: (P1) 20.3%, (P2) 31.25% and (P3) 6.77%; (P3 < P1, P2; p< 0.05). Intraoperative hypotension occurred more often in P3 (39%) compared to P2 (20.31%) and P1 (17.46%) (p< 0.05). Conclusion MMA + methadone was associated with higher incidence of intraoperative hypotension and lower incidence of moderate/severe pain in PACU after LBS.