Agile practices have empirically shown to increase adaptability, reduce lead times, reduce cost, increase quality, and increase employee morale for small software application teams. Scaled Agile expanded these benefits beyond teams to release trains and solution trains with thousands of people. I will leverage 26 years’ experience building safety-critical cyber-physical systems from submarines to satellites at Lockheed Martin as a senior technical fellow to explain why there is a need to expand these benefits to large scale, safety-critical cyber-physical systems with hardware, firmware, and software. We understand that there is a hesitation in highly regulated environments such as Aerospace, Automotive, Medical, and Energy due to concern that Agile practices conflict with safety regulations. I will present patterns of success in using Agile to build Cyber-Physical Systems that increase safety, security, reliability, and availability in large cyber-physical systems. My presentation demonstrates that there is an mission imperative to migrate from phase gate approached to Scaled Agile to increase safety for stakeholders. The bodies of knowledge that inform my presentation Scaled Agile, DevOps, Lean, Systems Thinking, Design Thinking, Digital Engineering, and Additive Manufacturing.