We pursued the use of regional analgesia (RA) to minimize the use of postoperative opioids. Our aim was to increase the use of postoperative RA for eligible surgical procedures in the NICU from 0% to 80% by June 30, 2019. A multidisciplinary team determined the eligibility criteria, developed an extensive process map, implemented comprehensive education, and a structured process for communication of postoperative pain management plans. Daily pain team rounds provided an opportunity for collaborative comanagement. An additional 30 minutes for catheter placement was added in operating room (OR) scheduling so that it would not affect the surgeon OR time. There were 21 eligible surgeries in the baseline period and 34 in the intervention period. In total, 30 of 34 infants in eligible surgeries (88%) received RA. The average total opioid exposure in intravenous morphine milligram equivalents decreased from 5.0 to 1.1 mg/kg in the intervention group. The average time to extubation was 45 hours in the baseline period and 19.9 hours in the intervention group. After interventions, 75% of infants were extubated in the OR, as compared with 10.5% in the baseline period. No difference was seen in postoperative pain scores or postoperative hypothermia between the baseline and intervention groups. We used quality improvement methodology to develop a structured RA program. We demonstrated a significant reduction in opioid requirements and need for mechanical ventilation postoperatively for those infants who received RA. Our findings support safe and effective use of RA, and provide a framework for implementation of a similar program.