Fostering a culture that empowers staff to speak up when concerned about the quality or safety of patient care is both an ethically1 and economically2 responsible endeavor. The Michigan Health & Hospital Association (MHA) Keystone Center has implemented the Speak-Up! Award program that acknowledges frontline health care staff for voicing their concerns and making care safer. The objective of this effort was to advance patient safety in Keystone Center member organizations through widespread, measurable culture improvement. After extensive data collection and analysis, there was a discernable improvement in culture survey results across a 2-year period coinciding with the launch and sustainment of the award program. Furthermore, in an effort to demonstrate the power of speaking up among staff, the Keystone Center applied a cost-savings framework to the types of harm avoided. Results from the cost-savings analysis suggest that each instance of speaking up by staff saves patients, families, and health care organizations an average of more than $13,000. Keystone Center Speak-Up! Award nominations were submitted through an electronic form that collects open, closed, and Likert-type question responses, producing a data array on type and severity of harm prevented, as well as the difficulty and magnitude of the decision to speak up. All data were then coded by harm type and subsequently applied to a tailored version of the cost-savings estimation framework used in the Great Lakes Partnership for Patients Hospital Improvement and Innovation Network. Safety culture was measured through the use of a survey instrument called the Safety, Communication, Operational Reliability, and Engagement (SCORE) instrument. The Keystone Center Speak-Up! Award program received 416 nominations across the 2-year study period, of which 62% (n = 258) were coded as a specific harm type. Adverse drug events (n = 153), imaging errors (n = 42), and specimen errors (n = 27) were the most common harm types prevented by speaking up. After applying the cost-savings framework to these data, it is estimated that for every instance of speaking up, approximately $13,000 in total expenses were avoided, which is in line with the findings from a report on the economic impact of medical errors sponsored by the Society of Actuaries.3 Furthermore, culture survey results improved by 6% between 2015 and 2017, coinciding with the Keystone Center Speak-Up! Award program. The Keystone Center Speak-Up! Award has proven to be a valuable tool in recognizing staff awareness and willingness to raise concerns about quality and safety in health care. Data analysis from this program presents evidence that fostering a psychologically safe culture of speaking up yields fiscal and humanistic returns, both of which are crucial to sustainable, meaningful progress in safety and quality. However, further research is required to adequately gauge the degree to which safety culture improvement is proportional to cost savings.