Despite significant advancements in safety, cardiopulmonary bypass (CPB) in open cardiac surgery remains a procedure prone to inherent mechanical complications. This chapter is designed to serve as a comprehensive guide, detailing the most significant and frequent mechanical complications associated with CPB. It focuses on identifying these complications, assessing the associated risks to patients, exploring their causes, and examining their clinical manifestations. Additionally, the chapter provides in-depth management strategies for these complications, addressing each element of the CPB circuit. Various CPB complications are extensively discussed, including arterial cannula displacement, tubing fracture or leakage, venous air lock, iatrogenic inferior vena cava injury, systemic gas embolism, circuit thrombus formation, reservoir overflow and depletion, runaway pump, pump electrical malfunction, arterial filter fracture, oxygenator dysfunction, sweep gas supply failure, and heater-cooler unit failure. To effectively address intraoperative CPB emergencies, the chapter advocates for a standardized emergency response protocol encompassing clear communication, resource mobilization, and postoperative debriefs for quality improvement.