Between July 2019 and September 2020, the California Maternal Quality Care Collaborative engaged 27 birthing facilities located in counties with high rates of neonatal abstinence syndrome to participate in its mother & Baby Substance Exposure Initiative (MBSEI) Collaborative based on AIM’s Opioid Use Disorder (OUD) patient safety bundle. These facilities represented 14% of live births in the state. Participating facilities identified and implemented best practices in areas including screening, treatment, transitions in care, and education for OUD. Among the MBSEI Collaborative hospitals, the proportion of pregnant people with OUD who received medication for opioid use disorder or behavioral health treatment increased from 45% in January 2019 to 58% in December 2020, representing a 29% increase. During the same period, the proportion of opioid-exposed newborns ≥35 weeks’ gestation who received any of their parent’s milk at discharge increased from 56% to 65%, representing a 16% increase. Long-term outcomes for birth parents and infants will continue to be assessed through other programs.