BACKGROUND: The serratus posterior superior intercostal plane block (SPSIPB) is a newly described truncal block. This study aimed to compare the effects of SPSIPB with conventional methods on postoperative opioid consumption and pain scores within 24 h postoperatively. METHODS: This randomized controlled trial included 60 patients aged 18-65 years with an American Society of Anesthesiologists Physical Status of I-III. Patients were randomly assigned to either the SPSIPB or the control group. The primary outcome was cumulative opioid consumption within the first 24 h postoperatively. Secondary outcomes included resting and dynamic Numerical Rating Scale (NRS) pain scores, Quality of Recovery (QoR)-15 questionnaire scores, intraoperative remifentanil consumption, and the incidence of postoperative nausea and vomiting. RESULTS: Total tramadol consumption was significantly lower in the SPSIPB group during the first 12 h and at the end of the 24th hour postoperatively compared with the control group (p <
0.05). The dynamic NRS score at 0 h postoperatively was lower in the SPSIPB group (p = 0.002), whereas no significant differences in NRS scores were observed at other time-points. The postoperative QoR-15 scores were significantly higher in the SPSIPB group compared with the control group. Furthermore, the SPSIPB group had significantly lower intraoperative remifentanil consumption (p = 0.003). Nausea and vomiting were more frequent at 12 and 24 h postoperatively in the control group compared with the SPSIPB group. CONCLUSIONS: Serratus posterior superior intercostal plane block significantly reduced opioid use, and improved recovery quality after oncoplastic breast surgery. TRIAL REGISTRATION: NCT06225908, registered at ClinicalTrials.gov.