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Background: del Nido cardioplegia has been adopted for use in adult cardiac surgery, despite a lack of robust randomised evidence supporting equivalence or superiority to conventional hyperkalaemic blood cardioplegia. We investigated the clinical surrogates of myocardial protection, and performed an extensive analysis of post‐operative high‐sensitivity Troponin T (hs‐TnT) values in a general adult cardiac surgery population receiving del Nido, in comparison to a historical hyperkalaemic blood cohort. Method: 171 consecutive patients of a single surgeon from between November 2018 and June 2020 received del Nido, and were compared to a historical cohort of 326 patients between January 2016 and November 2018 who received hyperkalaemic blood cardioplegia. Clinical markers of myocardial protection were compared, as were hs‐TnT values at 6, 12, 24, and 72‐h post‐operatively. Equivalence between groups was determined using the two one‐sided tests procedure. Results: There was no difference between the groups in the incidence of post‐operative low cardiac output state, inotropic support, or myocardial infarction. Del Nido patients had less defibrillation requirement, and more spontaneous resumption of normal sinus rhythm. High‐sensitivity Troponin T values were similar at all time‐points including in a coronary artery bypass graft subgroup, and in those patients with elevated pre‐operative hs‐TnT. Conclusion: In a broad cohort of adult cardiac surgery patients, including those undergoing coronary artery bypass surgery and those with recent myocardial infarction, del Nido provides equivalent myocardial protection and clinical outcomes when compared to hyperkalemic blood cardioplegia. Post‐operative high‐sensitivity Troponin T values were also equivalent between the groups. [ABSTRACT FROM AUTHOR]