The goal of a controlled clinical trial is to compare the effects of interventions on outcomes of interest. This chapter considers the methods to limit bias and random error at each stage of a clinical trial-design, conduct, analysis and interpretation of results. Many aspects of study design relate to control of bias. The one of greatest importance is the method of assignment to treatment. Study assessments that incorporate some element of subjectivity can also be centralized. Many trials rely on a central adjudication group to make outcome assessments for all subjects in a study. In most studies, the treatments are compared with regard to multiple outcomes. From sample size considerations to central pathology review, from eligibility reviews to interim monitoring plans, all methodological considerations relate in one way or other to minimizing the potential for bias and reducing random error.