Assessing the impact of publicly funded scientific research in entrepreneurial ecosystems is of great interest for science and entrepreneurship policy. Knowledge from academic research flows into the private sector through publications, patents, and researcher mobility as well as through direct interactions between founders and researchers at public research institutions (PRIs). New technology-based firms (NTBFs) are generally praised for high innovativeness despite their resource constraints and liability of newness. This study therefore investigates the impact of direct interactions with PRIs on NTBFs’ innovation success. In a large sample of NTBFs in Germany, we find that those firms engaging in such knowledge interactions are more likely to introduce new products and services to the market. The strength of this association, however, depends on interaction persistency, internal R&D and the founders’ academic backgrounds. Non-academic start-ups benefit more from continuous informal interactions if they pursue own R&D, which suggests that absorptive capacity matters. In academic start-ups, higher intensities of both formal and informal interactions are associated with greater innovation likelihood. Moreover, continuous informal interactions complement formal ones in the absence of own R&D activity.