Background: The Regional Systemic Treatment Program at Cancer Care Ontario (CCO) aims to ensure the highest quality of systemic treatment is available to Ontarians, as close to home as possible. CCO initiated a provincial collaborative with the aim of improving the safe delivery of parenteral chemotherapy from orders through preparation, to administration, for patients, and providers. Methods: From April 2011 to March 2012, interdisciplinary hospital teams across Ontario followed multiple Plan, Do, Study, Act cycles to perform QI projects focusing on safe delivery of systemic treatment. Over this period, three in-person sessions educating participants on improvement methodology were held. Monthly teleconferences and an electronic discussion forum encouraged a culture of knowledge sharing and collaboration. Results: 113 participants from 26 teams participated in a total of 81 improvement initiatives. 96% of participants surveyed indicated that the collaborative provided a valuable opportunity to network with peers, share ideas, and discuss lessons learned. During the collaborative, teams reported their progress on a scale of 1-5. At May 2011, teams averaged a self-assessment score of 1, indicating no progress had been made. By February 2012, this increased to an average score of 4, indicating significant progress and achievement of at least one improvement objective/goal. CCO has leveraged the foundations built by the collaborative to develop a Regional Quality and Safety Network. This network provides a regular forum for health care providers and administrators to share knowledge and collaborate on strategies for improving quality and safety in the delivery of systemic treatment. Conclusions: The collaborative demonstrated that the use of a formal quality improvement model is a successful mechanism for regional engagement; that provides the foundation necessary for building a provincial network with common goals and understanding regarding quality improvement. By educating participants, supporting local efforts and enabling knowledge transfer and exchange, the collaborative showed that shared ideas and even small changes can lead to large-scale improvements for patients and providers.