Study objectiveTo determine whether ultrasound-guided serratus anterior plane block (SAPB) is associated with decreased prevalence of chronic postsurgical pain (CPSP) after modified radical mastectomy. DesignRandomized, double-blind, placebo-controlled study. SettingUniversity hospital. PatientsWe enrolled 198 patients aged 18–65 years with American Society of Anesthesiologists physical status I to II, undergoing unilateral modified radical mastectomy. InterventionsPatients were randomly allocated to receive SAPB with 30 ml of 0.5% ropivacaine (SAPB group) or 0.9% normal saline (Control group). MeasurementsThe primary outcome was the prevalence of CPSP three months after surgery. Secondary outcomes were area under the curve of the numeric rating scale pain scores over 24 h, postoperative 24-h morphine consumption, quality of recovery, length of post-anesthesia care unit stay, postoperative nausea and vomiting, dizziness, SAPB-related adverse events, the prevalence of CPSP at six months, and pain-related function at three and six months. Main resultsPreoperative SAPB with 0.5% ropivacaine reduced the prevalence of CPSP at three postoperative months from 46/89 (51.7%) to 22/90 (25.6%), relative risk (95% confidence interval): 0.47 (0.31–0.72), P < 0.001. The prevalence of CPSP was reduced at six months from 37/89 (41.6%) to 17/90 (18.9%), relative risk (95% confidence interval): 0.72 (0.58–0.88), P = 0.001. Moreover, SAPB decreased the area under the curve of the numeric rating scale pain scores over 24 h, shortened the length of post-anesthesia care unit stay, reduced postoperative 24-h morphine consumption and the occurrence of postoperative nausea and vomiting, and improved quality of recovery and patient satisfaction, with P < 0.05 for all. No SAPB-related complications occurred. ConclusionsPreoperative SAPB with ropivacaine improved acute postoperative analgesia and quality of recovery and decreased the prevalence of CPSP at three and six months after modified radical mastectomy.