In our study, patients who underwent isolated coronary artery bypass surgery (CABG) using Del Nido cardioplegia (DNC) and crystalloid-based cold blood cardioplegia (CBC) were compared. In this study, two groups of patients who underwent isolated CABG using DNC (n = 106) and CBC (n = 107) were prospectively randomized. Groups were compared in terms of many results such as troponin T, returning spontaneous rhythm, and cardioplegia volume. Median troponin T levels of the DNC and CBC groups were compared for the 0th hour (baseline), 12th, 36th, and 60th hours. There was no statistical difference between groups in troponin T levels of the baseline 0th hour (18[33] vs. 22[27] pg/ml; P = 0.724). Troponin T levels at the 12th hour were less in the DNC group than the CBC group but no statistical difference between the groups (790[735] vs. 826[820] pg/ml; P = 0.068), respectively. Troponin T levels at 36th and 60th hours were higher in the CBC group compared to the DNC group, and a statistical difference was observed (580[546] vs. 650[550] pg/ml; P = 0.030) and (359[395] vs. 421[400] pg/ml; P = 0.020), respectively. After X-clamping, the spontaneous rhythm rate was statistically higher in the DNC group than the CBC group (72.60% vs. 37.40%; P < 0.001). There was no statistical difference between the groups in terms of postoperative arrhythmia, hospital stay, and mortality rates (P > 0.05). Based on data we acquired from the study, we think that DNC is at least as safe and effective as CBC in adult CABG cases.