This chapter provides an in-depth exploration of the complex strategies necessary to ensure patient safety in cardiac surgery. It focuses on the critical role of safeguards and checklists in the operation of cardiopulmonary bypass (CPB) machines. The chapter explores the complicated field of CPB-specific safety devices, both invasive and non-invasive, which act as essential protections from potential human error and technological malfunctions. These devices range from simple monitors to complex feedback loops, offering a safety net for perfusionists. They guard against inadvertent operational errors and swiftly alert to impending dangers, empowering perfusionists to confidently navigate the complexities of CPB. Beyond devices, the chapter highlights the essential role of effective communication in patient safety. Pre-procedure briefings, huddles, and handoffs contribute to a closed-loop safety system, where information flows seamlessly and every team member is a vital link. The power of checklists is examined in detail, showcasing their invaluable contribution to ensuring meticulous adherence to critical steps and reducing the risk of omissions. This equips perfusionists and the entire cardiac surgical team with the knowledge and tools necessary to prioritize patient safety at every stage, from the initial bypass connection to the final decannulation. This chapter underscores the importance of these protocols and devices in safeguarding patients, ensuring successful outcomes in cardiac surgery.