Higher Education is widely seen as a crucial ingredient in the regional economic development mix, and as fundamental to the development of the knowledge economy (Barclays, 2002). Indeed the Higher Education Funding Council for England has issued broad guidelines for benchmarking good practice in assessing regional development contribution of a higher education institution (HEFCE, 2002). However, there is a dichotomy between the view of higher education as an investment in regional development, and the common evaluative practice of simply assessing the cash-flow consequences of individual institutions. In contrast to the volume of standard impact assessments, there has been relatively little work that seeks to systematically evaluate the effect of higher education on regional development, or indeed to estimate either its net public purse impacts or its export value. This article draws on recent studies to seek to develop a realist evaluation framework that can provide the evidence-base to enhance both the higher education/regional development relationship, and policy making initiatives for the sector.