Statistical evidence suggests that the relevance of knowledge spillovers has increased over time. In this paper we focus on regional knowledge spillovers and adopt a new econometric transformation that allows inference on potential inter-regional knowledge spillovers, accounting for spatial interdependencies. Determinants of inter-regional knowledge spillovers are explained with a sample of 103 Italian provinces. We find that a region’s absorptive capacity, measured by local R&D expenditure and social capital, implies a reduction of outward knowledge spillovers. Identification is based on the use of Two Stages Least Squares and Fixed Effects estimates