In this chapter we outline the key principles in design and analysis of trials for mental health. The chapter focuses on randomized controlled trials as these are the gold-standard trial design, which minimizes confounding due to other factors and enables us to draw conclusions about the effectiveness of the intervention. Other key principles of trial design discussed in the chapter include methods to develop a clearly stated, testable research hypothesis, definition of well-defined outcomes, appropriate choice of the control condition, masking of providers and participants where possible, realistic sample size estimates, and appropriate data monitoring and statistical analysis plans. The chapter also outlines alternatives to the parallel arm superiority trial design, such as equivalence and non-inferiority trials, cross-over, stepped wedge, fixed adaptive, and patient preference trial designs.