Histidine-alpha-ketoglutarate (often as histidine-tryptophan-ketoglutarate, or HTK, solution) is primarily used as a cardioplegic and organ preservation solution in surgery, particularly in cardiac and transplant procedures. Scientific evidence supports its use in these settings due to its unique properties: histidine acts as a buffer to maintain pH, alpha-ketoglutarate serves as an energy substrate, and together they help reduce ischemia-reperfusion injury during periods when tissues are deprived of blood supply. Multiple clinical trials and systematic reviews have shown that HTK solution is effective in preserving organs and protecting myocardial and other tissues during surgery. It is commonly used in Europe and the United States for these purposes and is endorsed by various surgical guidelines. However, while its use for acute organ protection and healing immediately post-surgery is well established, there is limited evidence for its direct effect on long-term surgical wound healing outside these specific contexts. Nevertheless, for the perioperative protection of organs and tissues during complex surgeries, the scientific foundation for HTK solution's use is robust, leading to its widespread adoption in clinical practice.