Deciding upon the most appropriate methodological approach to adopt when designing a research study is an important consideration for a researcher. When reviewing published research it may appear that methodological selection is arbitrarily determined, rather than being based upon a sound set of principles. However, it is argued that methodological choices should be guided by a set of principles and beliefs about the purpose of the inquiry. As an example, the principles that guided the methodological choice of a multiple case study design to investigate the phenomenon of advanced nursing practice are presented. In addition, the key characteristics of designing and conducting multiple case studies are discussed and explained in the context of an on-going study. The use of this approach is encouraged as an additional and complementary method of scientific inquiry within the realm of nursing.