Based on a multiple case study research, the paper aims at providing some first evidence on the adoption of Open innovation and sustainability practices by innovative startups. The focus is on the underlying motivations and the potential effect on startup success of the combined adoption of both types of practices. Following a literature review, an in-depth qualitative analysis has been performed based on five innovative startups based in the Romagna area (Italy) and in the Republic of San Marino. Results highlight that motivations to Open Innovation adoption are classified in necessity-driven and opportunity driven, differentiating among the lifecycle phases. As for sustainability practices, two main attitudes are recognized in startups: reactive and proactive. Finally, no results on the interrelation between Open innovation and sustainability practices adoption can be found in the investigating sample, leaving room for further studies.