Minimally invasive extracorporeal circulation (MiECC) has been developed in an attempt to integrate all advances in cardiopulmonary bypass technology in one closed circuit that shows improved biocompatibility and minimizes the systemic detrimental effects of CPB. Despite well-evidenced clinical advantages, penetration of MiECC technology into clinical practice is hampered by concerns raised by perfusionists and surgeons regarding air handling together with blood and volume management during CPB. We designed a modular MiECC circuit, bearing an accessory circuit for immediate transition to an open system that can be used in every adult cardiac surgical procedure, offering enhanced safety features. We challenged this modular circuit in a series of 50 consecutive patients. Our results showed that the modular AHEPA circuit design offers 100% technical success rate in a cohort of random, high-risk patients who underwent complex procedures, including reoperation and valve and aortic surgery, together with emergency cases. This pilot study applies to the real world and prompts for further evaluation of modular MiECC systems through multicentre trials.