Calnan, Michael .W. and Hashem, Ferhana and Brown, P (2017) Health and Care Excellence) as it regulates the provision of expensive new drugs within the English NHS on cost-effectiveness grounds. Ostensibly this is a highly rational process by which the regulatory mechanisms absorb uncertainty but in practice decision-making remains highly complex and uncertain. This paper draws on ethnographic data interviews with a range of stakeholders and decision-makers (n=41), observations of public and closed appraisal meetings, and documentary analysis regarding the decision-making processes involving three different pharmaceutical products. The study explores the various ways in which different forms of uncertainty are perceived and tackled within these Single Technology Appraisals (STAs). Difficulties of dealing with the various levels of uncertainty were manifest and often rendered straightforward decision-making problematic.Uncertainties associated with epistemology, procedures, interpersonal relations and technicality were particularly evident. The need to exercise discretion within a more formal institutional framework shaped a pragmatic combining of explicit and informal, collective and individual, strategies and tactics to navigate through the layers of complexity and uncertainty in making decisions.2