Increasing attention in the project management literature is being paid to the theme of uncertainty: its origins and how it impacts projects (see for instance Atkinson, Crawford & Ward, 2006 and Perminova, Gustafsson & Wikstrom, 2008). The purpose of this exploratory study was to investigate the determinants and impacts of project uncertainty in the context of safety-critical industries in the United Kingdom. Seven current projects across two such safety-critical industries, civil nuclear and aerospace, were studied by means of in-depth interviews with senior project managers. The authors posit a framework, incorporating four determinants of uncertainty that are prevalent in large-scale projects in these sectors. The framework comprises project content, context, organisational capability and culture. We then explain how these four determinants of uncertainty may impact on the delivery of project outcomes. Future work is now required to test the validity of these preliminary conclusions against a larger sample size, and to compare the determinants and impacts of uncertainty on safety-critical projects in the context of locations other than the UK.