Myocardial protection during cardiac surgery is crucial for preventing ischemia-reperfusion injury and preserving myocardial function. Cardioplegia, a solution used to induce electromechanical cardiac arrest, is the fundamental method for myocardial protection during on-pump procedures. Del Nido cardioplegia, developed in the 1990s, has gained increasing popularity in adult cardiac surgeries over the past two decades. Del Nido cardioplegia is a crystalloid-based solution used to achieve depolarized arrest. Its mechanism of action also involves preventing intracellular calcium overload, a key driver of reperfusion injury. Numerous studies have evaluated the safety and efficacy of del Nido cardioplegia in adult cardiac surgeries, including coronary artery bypass grafting and valve procedures. Compared to standard blood cardioplegia, del Nido cardioplegia has demonstrated reduced hemodilution, transfusion requirements and shorter cardiopulmonary bypass times due to its extended arrest duration. Many studies have reported lower levels of myocardial injury biomarkers and improved myocardial functional recovery with del Nido cardioplegia. It has also been associated with reduced defibrillation requirements, which is attributable to the antiarrhythmic effects of lidocaine. While some studies have reported no significant differences in outcomes between del Nido cardioplegia and blood cardioplegia, others have favored del Nido cardioplegia in terms of myocardial protection, postoperative cardiac function, and perioperative morbidity. The choice between cardioplegia solutions remains subjective and dependent on surgeon preference and institutional practices. However, del Nido cardioplegia has emerged as an acceptable alternative to traditional cardioplegia, offering potential advantages in adult cardiac surgeries.