Background <p>To quantitatively evaluate and compare the relative efficacy of different chest wall fascial plane blocks in cardiac surgery via median sternotomy.</p> Method <p>This study was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses for Network Meta-Analyses (PRISMA-NMA) utilizing a frequentist network meta-analysis (NMA) method. Conclusions were drawn using a minimally contextualized framework of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.</p> Results <p>Twenty-four randomized controlled trials were retrieved from four databases. A total of 1366 adult patients were included, of whom 789 (57.8%) received one of five chest wall fascial plane block modalities. The primary outcome was 24-hour postoperative opioid consumption (converted as intravenous morphine in mg, <i>n</i> = 1159). With moderate confidence, erector spinae plane block (ESPB) plus patient-controlled analgesia (PCA) was more efficacious in reducing 24-hour postoperative intravenous morphine than PCA alone (Rank based on SUCRA = 1). Secondary outcomes included postoperative mechanical ventilation time and pain assessment scores (0, 12, and 24&#xa0;h after extubation) with 1186, 664, 1054, and 958 patients analyzed, respectively. Network meta-regression results across primary or secondary outcomes suggested that local anesthetic type and volume, injection timing, and a continuous block feature may contribute to the relative efficacy of chest wall fascial plane blocks.</p> Conclusions <p>ESPB plus PCA was found to be more efficacious in decreasing postoperative opioid requirements for adults undergoing cardiac surgery via median sternotomy, with moderate confidence in the current evidence. Modifying the current fascial plane block protocols may be the direction of future clinical studies.</p> Trial registration <p>PROSPERO identifier CRD42022345047.</p>