The erector spinae plane block (ESPB) has recently emerged as a regional anesthesia technique for perioperative pain management in pediatric cardiac surgery. However, evidence comparing its effectiveness with intravenous (IV) opioid-based analgesia is limited. We aimed to evaluate and compare the analgesic efficacy of ESPB versus IV opioids in this setting. We systematically reviewed and meta-analyzed studies comparing ESPB with IV opioid analgesia in pediatric cardiac surgeries with midline sternotomy. Primary outcomes were intraoperative fentanyl consumption and intensive care unit (ICU) length of stay (LOS). Secondary outcomes included postoperative opioid consumption, time to first rescue analgesia, pain scores, postoperative vomiting and other complications, extubation time, and hospital LOS. Statistical analyses were performed using RStudio version 4.2.3. Five studies with 384 patients were included, with 178 receiving ESPB. ESPB significantly reduced intraoperative fentanyl use (MD -1.90 μg.kg-1; 95% CI -3.15 to -0.66 μg.kg-1; p = .003; I2 = 58%) and ICU LOS (MD -3.50 h; 95% CI -4.32 to -2.69 h; p < .0001; I2 = 0%). No significant differences were found in the remaining outcomes. Our findings suggest the ESPB might be an important adjunct to enhancing analgesia for midline sternotomies in pediatric cardiac surgery, potentially reducing intraoperative opioid requirements and ICU LOS. CRD 42024526961.