Beginning in 2003 the Gordon and Betty Moore Foundation partnered with fifty-three hospitals in the San Francisco Bay and Greater Sacramento areas of California to improve patient safety. The twelve-year, $167 million Betty Irene Moore Nursing Initiative was intended to empower front-line registered nurses (RNs) as leaders in implementing evidence-based clinical practices at the bedside. The initiative funded clinical efforts across seventeen patient safety improvement areas; results from seven of these are presented here. Bay Area hospitals had varied participation rates in those seven areas in the period 2006–13. For example, 14 percent of the hospitals participated in the effort to reduce acute myocardial infarction mortality, while 100 percent participated in the effort to reduce falls with injury. Patient outcome improvements compared to baseline also varied. For example, 43 percent of participating hospitals reported reductions in patient falls with injury, while 100 percent of hospitals participating in the effort to reduce medication administration errors reported improvements. Participating hospitals are maintaining the quality improvement outcomes that the foundation’s support helped them achieve. This shows the potential of front-line RNs to lead sustainable quality improvement efforts.