Whether the current post-16 qualifications system in the UK is fit for purpose has long been under discussion, with many calling for a broader, more interdisciplinary approach to preparation for university. This paper examines the relationship between post-16 (A-level) qualifications and degree success for students on the University of Exeter's innovative Natural Sciences programme, with particular emphasis on whether it is possible to be successful at degree level in subjects not studied at A-level. Maths was found to be the best predictor of success in interdisciplinary science and no one science was found to be more important than the others for preparing students for the bespoke interdisciplinary first year of the degree programme. The data also demonstrates that these students can be successful in later years in subjects not studied at A-level which they would otherwise have been prohibited from studying at university through their lack of core entry requirements. We acknowledge the unique nature of the cohort under analysis and the fact they self-select for this type of programme, but discuss how the study provokes questions and debate about pre-university qualification requirements and the way we structure our school and university curricula to maximise the opportunities for the next generation of STEM graduates.