Purpose <p>In laparoscopic surgery, balancing effective analgesia with preservation of pulmonary function remains a clinical challenge. Butorphanol, a κ-opioid receptor agonist and partial µ-opioid receptor agonist, may offer advantages in respiratory protection and anti-inflammatory effects.</p> Methods <p>This prospective, randomized, double-blind, three-arm, single-center clinical trial was conducted at the Affiliated Hospital of Zunyi Medical University. Between June 2021 and December 2023, a total of 81 patients undergoing elective laparoscopic surgery were enrolled, including 28 in the control group, 27 in the low-dose butorphanol group (1&#xa0;mg), and 26 in the high-dose butorphanol group (2&#xa0;mg). All patients received an intramuscular injection of the assigned study drug 30&#xa0;min before anesthesia induction. The primary outcome was intraoperative pulmonary gas exchange, including arterial partial pressure of oxygen (PaO₂), arterial partial pressure of carbon dioxide (PaCO₂₂), and end-tidal carbon dioxide (ETCO₂). Secondary outcomes included intraoperative ventilatory mechanics, perioperative pulmonary function, inflammatory markers, postoperative analgesia, anesthetic drug consumption, and follow-up outcomes up to 9 months after surgery.</p> Results <p>Compared with the control group, butorphanol—particularly at 2&#xa0;mg—significantly improved intraoperative pulmonary gas exchange. The high-dose group showed greater benefits in reducing airway pressures and anesthetic requirements, improving postoperative pulmonary function, suppressing inflammatory responses, and enhancing analgesic effects. During the 9-month follow-up, 70 patients completed all assessments, and the high-dose group consistently demonstrated superior recovery of pulmonary function, better quality of life, and lower levels of chronic pain.</p> Conclusion <p>Pre-induction butorphanol enhances intraoperative pulmonary gas exchange and improves secondary outcomes, with 2&#xa0;mg showing the most consistent benefits for ERAS protocols.</p> Clinical trial registration <p>The study has been registered with the Chinese Clinical Trial Registry, registration number: ChiCTR2100047900. Registration date: June 27, 2021. Not retrospectively registered.</p> Graphical Abstract <p>High-Dose Butorphanol Improves Postoperative Lung Function, Reduces Inflammatory Factors IL-6, IL-8, and TNF-α, and Enhances Analgesic Effects.</p> <p></p>