Objective <p>To compare the effects of liposomal bupivacaine and ropivacaine for ultrasound-guided parasternal block combined with rectus sheath block (PSB + RSB) on acute and chronic postoperative pain in patients undergoing cardiac sternotomy, so as to provide an evidence-based basis for optimizing the multimodal analgesia regimen for such surgeries.</p> Methods <p>A total of 90 patients scheduled for elective median sternotomy cardiac and great vessel surgery at the Institute of Cardiovascular Diseases, The First Affiliated Hospital of Guangxi Medical University from April 2024 to February 2025 were enrolled. They were divided into the liposomal bupivacaine group (group LB, n=45) and the ropivacaine group (group ROP, n=45) using the random number table method. After endotracheal intubation under general anesthesia, group LB was given 40 mL of 266 mg liposomal bupivacaine injection for bilateral PSB+RSB, while group ROP was administered 40 mL of 0.375% ropivacaine injection for the same block regimen.The following outcomes were recorded at different postoperative time points: cumulative consumption of analgesic drugs (calculated as morphine milligram equivalents, MMEs), scores of Numeric Rating Scale (NRS, 0-10 points) for pain assessment, scores of Quality of Recovery-15 (QoR-15) scale, and the incidence of adverse events.</p> Results <p>A total of 88 patients completed the study (2 patients in group LB were excluded due to surgical duration exceeding 8 hours). At 24 h and 48 h after the first postoperative awakening, the cumulative MMEs consumption in group LB was significantly lower than that in group ROP [55.30(47.80,62.10) vs 68.00(48.40,80.00) mg, 76.30(68.80.83.10) mg vs 86.00(63.40,119.60), all P &lt; 0.05]. At 4 h and 12 h post-extubation, the activity-related NRS scores in group LB were significantly lower than those in group ROP [2.00(2.00.2.00) points vs 2.00(2.00,3.00) points, 2.00(2.00,3.00) points vs 3.00(2.00,4.00) points, all P &lt; 0.05]. At 24 h, 48 h and 72 h post-extubation, the QoR-15 scores in group LB were significantly higher than those in group ROP [(85.4±11.78) points vs (74.7±9.89) points, (91.6±10.4) points vs (86.8±8.6) points, (107.1±9.87) points vs (100.0±9.15) points, all P &lt; 0.05]. The incidence of postoperative nausea and vomiting in group LB (16.3%, 7/43) was significantly higher than that in group ROP (2.2%, 1/45) (P &lt; 0.05). There were no significant differences between the two groups in postoperative endotracheal extubation time, ICU stay time, hospital stay, and the incidence of chronic postsurgical pain (CPSP) at 3 months after surgery .</p> Conclusion <p>The use of liposomal bupivacaine for PSB+RSB block in patients undergoing cardiac sternotomy can significantly reduce postoperative analgesic consumption, optimize early analgesic effect, and improve postoperative recovery quality. However, attention should be paid to the risk of nausea and vomiting, and individualized selection should be made after balancing the benefits and risks in clinical application.</p> Trial registration <p>Trial registration:This trial was registered in the Chinese Clinical Trial Registry (ChiCTR2400084078) on May 10, 2024 (<a href="https://www.chictr.org.cn/">https://www.chictr.org.cn/</a>).</p>