Background and aim of the study: Several studies reported safety and potential benefits of single dose Del Nido cardioplegia (DNC) in selected Adult Cardiac Surgery (ACS) procedures. However, studies are scarce on routine use of DNC in more complex procedures and patients with high risk profile. We sought to compare DNC with cold blood cardioplegia (BC) in all types of ACS including complex procedures. Methods: Data for 305 consecutive unselected patients who underwent ACS procedures (July/2017 to Nov/2019) were included. DNC was routinely used whenever is available (n=231) and if not available, cold BC is used (n=74). All categories of ACS procedures (primary or redo) were included. Repeated measures analysis was performed to compare baseline, peak and trough Troponins levels in both groups. Linear regression analysis was used to identify independent predictors of peak Troponins level. Results: The two groups were comparable in baseline characteristics including euro score (ES II), risk profile and surgical complexity. DNC was associated with lower cardiopulmonary bypass (CPB) and cross clamp times, cardioplegia volume and number of cardioplegia doses (P<.001). Importantly, DNC was associated with lower postoperative Troponin level (P=.001), shorter duration of inotropic support (P=.02) and shorter intensive care unit stay (P=.04). On linear regression analysis, DNC was an independent predictor of lower postoperative peak Troponin (t = -3.5, P<.001). Conclusions: Routine use of DNC in all types of ACS procedures compared to BC was associated with significantly shorter CPB and clamp times, significantly lower post-operative troponin release and shorter duration of inotropic support.