Background Launched in 2012, the Children's Hospitals' Solutions for Patient Safety (SPS) Network is a collaborative of children's hospitals in the United States and Canada working together to eliminate patient and employee/staff harm across all children's hospitals. Methods The SPS Network, which has grown from 8 to 137 hospitals, has a foundation of leadership engagement, noncompetition, data-driven learning, attention to safety culture, family engagement, and transparency. The SPS Leadership Group, which consists of more than 150 leaders from participating hospitals, forms condition-specific teams to promote the reduction of hospital-acquired harm in a phased design that includes an ongoing focus on both process improvement and safety culture enhancements. Hospital leaders are engaged through monthly reports, executive webinars, in-person meetings, and biannual training opportunities for boards of trustees. SPS has developed extensive opportunities for learning collaboration, including in-person networkwide learning sessions, regional meetings, general and condition-specific webinars, communications, and a shared website. Results Over time, the portfolio has expanded as SPS has achieved harm reduction targets for some conditions and begun work to reduce harm in other, previously unaddressed areas. In 2017 SPS reported a 9%–71% reduction in eight harm conditions by an initial cohort of 33 hospitals. SPS estimates that more than 9,000 children have been spared harm since 2012, with $148.5 million in health care spending avoided. Conclusion Participation in the SPS Network has been associated with improved safety in children's hospitals. Widespread participation in this or similar collaborations has the potential to dramatically decrease harm to patients, employees, and staff.