Low cardiac output syndrome and the systemic inflammatory response are consequences of the cardiac surgical perioperative course. The mechanisms responsible are multifactorial, but recent studies have shown that nitric oxide (NO) may be a key component in mitigating some of these processes. Following on from literature reports detailing the use of inhaled NO added to the gas phase of the extracorporeal circuit, we set about developing a technique to perform this addition safely and efficiently. In the setting of cardiopulmonary bypass, the technique was validated in a randomized prospective trial looking at 198 children. The benefits observed in this trial then stimulated the incorporation of NO into all extracorporeal life support (ECLS) circuits. This required additional hardware modifications all of which were able to be performed safely. Initial results from the first series of ECLS patients using NO also appear promising.