Background Intraoperative myocardial preservation is essential in pediatric cardiac surgeries. The combination of hypothermia and hyperkalemic cardioplegia is commonly used. Histidine-tryptophan-ketoglutarate (HTK–Custodiol) is a long-acting crystalloid cardioplegia which induces cardiac arrest by reducing the extracellular sodium concentration. Cold blood cardioplegia has many modifications differing in the blood: crystalloid ratio, buffers, substrates, and final potassium concentration which induces cardiac arrest in diastole as the main role. We compared cold histidine-tryptophan-ketoglutarate crystalloid (HTK) solution with hypothermic hyperkalemic blood (HHB) cardioplegia solution regarding their efficacy in myocardial preservation in patients undergoing total repair of non-cyanotic congenital cardiac defects. We assessed postoperative cardiac troponin level, myocardial function, inotropic support, intensive care unit (ICU) length of stay, hospital length of stay, and the incidence of prolonged postoperative mechanical ventilation as indicators of myocardial protection. Results This interventional, single-blinded, randomized, comparative, and prospective clinical study was conducted randomly on 60 patients, aged between 6 and 24 months undergoing total surgical repair. We found no statistically significant difference regarding patients’ personal, demographics, and operative details (surgery duration, cardiopulmonary bypass time, aorta clamp time). However, patients who were given HTK cardioplegia were found to stay less in the ICU (with a p value <0.05). However, there was no statistically significant difference between both groups as regards hospital length of stay. Also, all patients were extubated in less than 24-h duration. There was a statistically significant difference between both groups regarding troponin levels after 8, 12, and 24 h post-bypass in favor of the HHB solution. Interestingly, no significant correlation was proved between both groups regarding myocardial function (EF%, FS) and level of inotropic support (assessed by maximum vasoactive inotropic score). Conclusions Hypothermic hyperkalemic blood cardioplegia showed better results in myocardial preservation than the cold histidine-tryptophan-ketoglutarate solution in the repair of noncyanotic congenital cardiac defects. Trial registration Pan African Clinical Trial Registry, PACTR202109777317416. Registered on 28 September 2021—Retrospectively registered, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=16154