ObjectiveSuicide rates in the United States have risen dramatically during the 21st century despite national, state and local level commitments to prevention, improvements in the development and delivery of evidence-informed prevention approaches, and advances in epidemiological capacity to identify areas for targeted intervention. Complex problems require comprehensive solutions. In Colorado, that solution is a comprehensive, integrated public health collaboration that aligns diverse community and programmatic efforts across the prevention continuum. The Colorado National Collaborative (CNC) is pursuing a real-world test of the public health approach to suicide prevention by helping community coalitions deliver a package of evidence-informed activities in geographically defined community systems. MethodsThe CNC began by identifying six diverse Colorado counties with high suicide rates or number of deaths. Working closely with community, state, and national partners, CNC identified existing community-level risk and protective factors, programs, and policies. This process provided insight on the overlay between existing efforts and identified burden centers and drivers. ResultsThe CNC team identified six components for strategic implementation: (1) connectedness, (2) economic stability and supports, (3) education and awareness, (4) access to suicide safer care, (5) lethal means safety, and (6) postvention. Evaluation is being conducted through a collaborative, participatory, and empowerment approach that incorporates stakeholders as leaders in all aspects of the process. ConclusionThe CNC includes data-driven identification of populations at risk of suicide, community identification of protective factors, and true collaboration between prevention experts at the national, state, and local level in implementing a comprehensive approach to prevention. Lessons learned are discussed.