This chapter explores clinical trials, the gold standard in evaluating healthcare interventions. It begins by outlining the fundamental principles of randomisation, blinding, and control groups, which reduce bias and strengthen causal inference. Different trial designs, including parallel, crossover, cluster, and adaptive trials, are described, each with their advantages and limitations. Outcome measures, intention-to-treat analysis, and ethical considerations are discussed, highlighting the need for rigorous methodology and participant protection. The chapter considers both explanatory trials, which evaluate efficacy under ideal conditions, and pragmatic trials, which assess effectiveness in real-world practice. Challenges such as recruitment, adherence, attrition, and generalisability are addressed. Practical examples illustrate the transformative impact of clinical trials in areas such as cardiovascular medicine, oncology, and mental health. The role of data monitoring committees, trial registration, and reporting standards (CONSORT) is emphasised as essential for transparency and credibility. The chapter concludes by noting the continuing evolution of trial methodology, including adaptive designs and real-world evidence generation. This chapter maps to syllabus sections 3.2.11–3.2.12, which cover randomised controlled trials, intention-to-treat analysis, and trial design methodology.