To compare del Nido cardioplegia (DNC) with conventional blood cardioplegia (BC) in aortic root surgery.Subjects who underwent aortic root surgery during a 3-year period were included. A DNC group was compared with a matched BC group.A total of 72 subjects were included, 36 who underwent DNC compared with 36 propensity-matched subjects who underwent BC. Fifty-one (70.8%) were male, and 21 (29.2%) were female, with a mean age of 66.19 ± 7.02 years (range 51 to 81). No significant differences in baseline characteristics, preoperative echocardiogram parameters, or intraoperative parameters were found between the groups. For DNC versus BC, cardiopulmonary bypass time, aortic clamp time, cardioplegia volume (all P = .001), and defibrillation (P = .007) were significantly lower. For postoperative biochemical parameters, creatinine levels at hour 24, potassium levels at hours 1 and 24, and glucose levels at hours 6 and 24 did not differ between the groups (P > .05). Creatine kinase-MB and troponin T levels at hours 1 and 24 were significantly lower in DNC versus BC (all P = .001). Hematocrit levels at hours 6 and 24 were significantly higher in DNC (P = .001). The groups did not differ in terms of postoperative inotropic support, postoperative complications, intubation period, or duration of intensive care unit stay (P > .05). Although the need for thrombocyte transfusion did not differ between groups (P > .05), DNC resulted in less use of erythrocyte and fresh frozen plasma transfusions (both P = .001). Postoperative ejection fraction was significantly better in the DNC group than in the BC group (P = .006).The results indicate better intraoperative parameters and better ejection fraction rates with DNC than with BC. DNC is an effective and safe alternative to blood cardioplegia for aortic root surgery.