Health Impact Assessment (HIA), an inherently trans-disciplinary approach, is used to help evaluate and improve projects or programmes in sectors such as transportation, where new infrastructure is likely to have effects on health. This article describes the screening, scoping, appraisal, and recommendation steps of an HIA on a new 24 km highway around the conurbation of Strasbourg, France. Methods included a literature review and quantitative estimates of the health effects of air pollution and noise. Although planned, interviews and focus groups proved impossible due to political and administrative difficulties. In replacement, answers to a related public inquiry were submitted to a secondary, thematic analysis. The new infrastructure is likely to create or help maintain some jobs in the short term and might accelerate certain journeys, but it does not seem able to improve local mobility and air quality issues. It crystallises the dissatisfaction of a part of the local population and raises the question of the transparency of the design and validation processes of major infrastructure projects. Despite an unfavourable political context, the HIA approach described in this article was able to overcome methodological difficulties and obstacles thanks to creative research methods and trans-disciplinarity to finally yield relevant information and suggestions for urban health promotion.