This chapter, The Ethics of Medical Research in Surgery by Claudio S. Cinà, addresses the complex ethical issues involved in human and animal surgical research, the methodology, and the risk of conflicts of interest. It reflects on the ethical problems resulting from the invasive nature of surgery and reliance on living recipients, the difficulty of performing randomized controlled trials (RCTs), and the role of alternative approaches for the generation of solid evidence to support the advancement in clinical practice. The basic principles of human research, such as informed consent, autonomy, and transparency, are protected by Institutional Review Boards (IRBs). Animal research is regulated by the fundamental principles referred to as the Three Rs, Replacement, Reduction, and Refinement, under the guidelines of the Institutional Animal Care and Use Committees (IACUCs), supplemented by the reporting requirements of the ARRIVE guidelines. To prevent conflicts of interest and bias and maintain the highest standards of integrity, it is essential that strong guidelines and strict supervision are adopted. Finally, this chapter maintains that sound methodologies, clear reporting, and strong ethical oversight work synergistically to advance surgical progress while maintaining the dignity and well-being of all experimental subjects.