Simultaneous application of pectoral nerve block and serratus-intercostal plane block (SPB) is one of the most desirable multimodal analgesic strategies, with wide implementation of the enhanced recovery after surgery pathway for modified radical mastectomy (MRM).The aim of the present study was to investigate the efficacy and safety of ultrasound-guided pectoral nerve block I (PECS I) and SPB for postoperative analgesia following MRM.A randomized, prospective study.An academic medical center.A total of 61 women undergoing MRM were randomly divided into 2 groups. The control group (group C, n = 32) received general anesthesia only, whereas the PECS I + SPB treated group (group PS, n = 29) received a combination of pectoral nerve block and SPB in addition to general anesthesia.Pain scores on a visual analog scale, opioid consumption, the duration at the postanesthesia care unit, and the incidence of adverse events were lower in group PS, compared with that of the group C. Moreover, PECS I together with SPB contributed to better sleep quality and higher patient satisfaction of pain relief.This study was limited by its sample size.These results suggest that the combination of PECS I and SPB provide superior perioperative pain relief in breast cancer surgery.Pectoral nerve block, serratus-intercostal plane block, postoperative analgesia, modified radical mastectomy.