Despite the deeply rooted belief of politicians all over the world about the important role of Mittelstand firms, there has yet been surprisingly little empirical research on this issue. This article contributes to the literature by studying whether the relative regional importance of Mittelstand firms has an effect on regional innovation performance. Using a cross-section of German NUTS-3 regions, a significantly positive relation between the relative importance of owner-managed small and medium-sized enterprises and patent applications is identified. This finding is highly robust when controlling for spatial correlations as they often occur in highly disaggregated regional analyses.