Background and Aims The immediate postischemic period is marked by elevated intracellular calcium levels, which can lead to irreversible myocyte injury. Del Nido cardioplegia was developed for use in the pediatric population to address the inability of immature myocardium to tolerate high levels of intracellular calcium following cardiac surgery. Our aim in this study is to determine if this solution can be used safely and effectively in an adult, reoperative population. Methods All patients undergoing isolated reoperative aortic valve replacement at our institution from 2010 to 2012 were retrospectively reviewed. Demographics, comorbidities, operative variables, postoperative complications, and patient outcomes were collected. Patients were divided into two groups based on cardioplegia strategy used: whole blood cardioplegia (WB, n-=-61) and del Nido cardioplegia (DN, n-=-52). Results Mean age in the study was 73.4-±-14.3 years and 86 patients were male (76.1%). Eighty-four patients had undergone prior coronary artery bypass graft (CABG) (74.3%). Patients in the DN group required significantly lower total volume of cardioplegia (1147.6-±-447.2-mL DN vs. 1985.4-±-691.1-mL WB, p-<-0.001) and retrograde cardioplegia dose (279.3-±-445.1-mL DN vs. 1341.2-±-690.8-mL WB, p-<-0.001). There were no differences in cross-clamp time, bypass time, postoperative complication rate, or patient outcomes between groups. Conclusions Del Nido cardioplegia use in an adult, reoperative aortic valve population offers equivalent postoperative outcomes when compared with whole blood cardioplegia. In addition, use of del Nido solution requires lower total and retrograde cardioplegia volumes in order to achieve adequate myocardial protection. doi: 10.1111/jocs.12360 (J Card Surg 2014;29:445-449) © 2014 Wiley Periodicals, Inc.