Purpose: The use of del Nido cardioplegia in adult cardiac surgery is increasing. This study evaluated the use and clinical outcomes of del Nido cardioplegia (DNC) versus hyperkalaemic blood cardioplegia (HKB) in adult cardiac surgery. Methodology: Retrospective, multicentre study across Australia and New Zealand in adult patients undergoing cardiac surgery between 2018 and 2023. Data was obtained from the Australian and New Zealand Collaborative Perfusion Registry (ANZCPR). Since collection of DNC data, 13,809 patients underwent cardiac surgery for coronary artery bypass grafting (CABG), valve replacement and combined valve/CABG surgery. Patients receiving either DNC or HKB were propensity matched 1:1 based upon age, sex, pre-operative left ventricular function, NYHA status, diabetes, respiratory disease, peripheral vascular disease, hypertension, EUROscore, and hospital. A subgroup propensity matched analysis was performed on CABG only patients. Post operative mortality, morbidity and combined morbidity (ventilation greater than 48 hr, post operative renal injury, stroke, return to theatre, and deep sternal wound infection). Results: A total of 3434 propensity matched patients were identified (1717 in each group). The groups were well matched regarding comorbidities, median age 67 years, 26% female. Death (1.3% DNC vs 1.9% HKB), combined morbidity outcomes (14% vs 13.2%) and acute kidney injury (RIFLE class 1 or greater) were similar in each group (p>0.05). Equivalence testing of main outcomes (death, new renal failure, prolonged mechanical ventilation, stroke and return to theatre) found DNC to be equivalent to HKB (p<0.001). Analysis of CABG only patients found similar results. Conclusion: In propensity matched adult cardiac surgery patients, comparable perioperative morbidity and mortality were observed with the use of del Nido cardioplegia compared with hyperkalaemic blood. There was no significant difference between groups for any post operative outcomes.