Quebec's health network has undertaken large-scale organizational changes to ensure the continuity, accessibility, and quality of health care and services for the population. This article describes the optimal approach for making changes to the organization of care and work for patients, health care workers, and organizations. This participative action research was carried out by means of interviews and document analysis. One hundred participants were involved, describing a total of 34 projects for significant organizational change. Results include an optimal approach broken down into 4 phases, each of which includes steps, facilitating factors, and potential difficulties. The phases of this approach are: (1) sharing the vision, mission, and values of the organization and identifying the purpose and need underlying the change; (2) building alliances and validating the involvement of the various players; (3) conceptualizing and planning the project; and (4) implementing changes and continuing evaluation. It is possible to rise to the challenge of finding new approaches to organize care and work by giving way to participation, mobilization, and innovation.