Design validation is an integral aspect of the systems engineering process and safety reviews. In the nuclear industry, integrated system validation (ISV) is the primary means of validating the human factors aspects of new and modified plant designs. However, challenges posed by ISV have led to interest in alternative approaches to validation. One alternative is multi-stage validation (MSV), which involves conducting validations at multiple points throughout the design process. The objective of this research was to define MSV and to identify its potential benefits, methodology, and technical issues and challenges. To address this objective, we reviewed standards and guidelines, case studies of design validation using MSV approaches, and technical literature discussing MSV methodology. From this technical basis we developed a characterization of MSV. The general goal of validation is to provide evidence that a design or design-related activity achieves its intended purpose. MSV approaches to validation achieve this goal by linking validation activities to design stages resulting in incremental, successive validation activities beginning in the early stages of the design process and continuing through the late stages of the design process. The main elements of an MSV program are: Determining the scope of MSV, identifying stages, developing MSV methodology, integrating MSV results across validation tests, and formulating validation conclusions. MSV has many challenges and benefits when compared with ISV alone. Further development of MSV methodology will help minimize MSV’s challenges and provide designers and regulators with guidance needed to implement and review MSV programs.