The complexity of innovation processes implies the necessity of undertaking collaboration between innovation active enterprises, scientific and research units, clients, suppliers, consulting units, and the regional authorities. The benefits obtained through this interorganisational collaboration should contribute to an increased effectiveness of innovation activity. The paper aims at empirical evaluation of the relation between collaboration on innovation activity and the effectiveness of this activity in the EU regions. The data for the analysis were extracted from the EU Regional Innovation Scoreboard. The research sample covered 234 European regions from 23 countries over the period 2007-2016. In order to achieve the aim of the paper, the cross-sectional analyses of parametric and non-parametric correlations between the normalised variables representing the share of collaborating innovative small and medium-sized enterprises (SMEs) and diverse measures of innovation output, including: EPO patent applications, share of SMEs introducing innovations (product, process, marketing or organizational) and the sales of new-to-market and new-to-firm innovations as a percentage of total turnover. Given the likely multi-dimensional interdependencies and feedbacks between the enablers of innovative processes, intensity of innovative activities in the business sector, and their final outcomes, the investigated associations were additionally tested using the partial correlation analysis for the impact of selected control variables regarding the human capital and R&D activities. The results of the investigation indicate that, in general, regions characterised with more intense collaboration between innovative enterprises tend to exhibit higher effectiveness of innovative activities, as indicated by the positive and statistically significant correlations between the share of collaborating innovative SMEs and the key innovation output indicators of the EU regions. These results confirm a crucial role of collaboration in a successfully accomplished innovation process and imply the necessity of creating favourable conditions for the interactions between innovation-active entities. A key part in this field should be assigned to the regional authorities, which should facilitate the emergence of the networks of collaboration by using the appropriate mechanisms and instruments of regional and innovation policies.