This article shares the experiences of a new institute for patient safety and quality in Asia in building an organization culture of patient safety. Since its launch in June 2017, the SingHealth Duke-NUS Institute for Patient Safety & Quality in Singapore has been active in integrating cluster-wide efforts in patient safety and quality within the SingHealth Duke-NUS Academic Medical Centre. Institute for Patient Safety & Quality focuses on eliminating preventable errors and harm, and improving patient outcomes by building and cultivating a strong patient safety culture. A culture where healthcare professionals strive for implementation of strong safety management systems requires strong leadership, which prioritizes safety above financial and operational goals; encourages the identification, communication and resolution of safety issues and provides appropriate resources, structure and accountability to maintain effective safety systems. A strong patient safety and quality culture requires a virtuous patient safety and quality ecosystem that takes time to develop. We believe that it is necessary when building this ecosystem to promote the various contributing constituent cultures, including Speak Up Culture, Reporting Culture, Learning Culture, Patient Centric Culture and Just Culture. Leadership commitment is paramount for developing this ecosystem. This entails co-creation of organizational strategies and co-development of a professional education framework to enhance capability and capacity for patient safety and quality.