Since the emergence of the Evidence-Based Medicine (EBM) movement, the nature and role of evidence in medicine has been much debated. The formal classification of evidence that is unique to Evidence-Based Medicine, referred to as the Evidence hierarchy, has been fiercely criticized. Yet studies that examine how Evidence is classified in EBM practice are rare. This article presents an observational study of the nature of Evidence and Evidence-Based Medicine as understood and performed in practice. It does this by examining how an absence of Evidence is defined and managed in Evidence-Based Guideline development. The EBM label does not denote the quantity or quality of evidence found, but the specific management of the absence of evidence, requiring a transparently reported process of evidence searching, selection and presentation. I propose the term ‘Evidence Searched Guidelines’ to better capture this specific way of ‘being’ EBM. Moreover, what counts as Evidence depends not just on the Evidence hierarchy, but requires agreement between the members of each guideline development group who mobilize a range of ‘other’ knowledges, such as biological principles and knowledge of the clinic. In addition, I distinguish four non-Evidentiary justifications that are relied upon in the formulation of recommendations (literature, qualified opinions, ethical principles, and practice standards). These are not always secondary to Evidence but may be positioned outside the hierarchy, allowing them to trump Evidence. The legitimacy of Evidence-Based Medicine relies neither on experts nor numbers, but on distinct procedures for handling (non-)Evidence, reflecting its ‘regulatory objectivity’. Finally, the notion of transparency is central for understanding how Evidence-Based Medicine regulates, and is regulated within, contemporary biomedicine.