This paper offers an in-depth analysis of the characteristics of innovative start-up firms in Friuli-Venezia Giulia, an autonomous region situated at the extreme North East of the Italian territory, bordering with Austria and Slovenia. This work is part of a series of thematic papers on sub-national start-up landscapes in Italy, produced by the OECD Trento Centre for Local Development. Following the 2018 OECD Evaluation of the Italian Start-up Act, which embraced a national perspective, it represents a first attempt to analyse the impact of this policy at the local level. Friuli-Venezia Giulia hosts a polycentric, mainly urban start-up landscape, with a low prevalence of female and young founders. Its historical sub-regions of Friuli and Venezia Giulia present remarkable differences under several perspectives, including the industrial composition of their start-ups, the spread of emerging technologies among them and their propensity to use national incentives. Firm dynamism, notably high-growth and exit trends, constitutes another major focus of this work, which concludes with a set of evidence-based recommendations for policy-makers.