This paper discusses how the policy mix concept applies to RIS3. The paper argues that the RIS3 implementation phase – and the development of an efficient policy mix supporting RIS3 orientations – is at least as important as the design phase. Countries and regions are now embarking on the implementation phase of the RIS3. If a sequential approach is taken, disconnecting design and implementation, RIS3 will not be effective as they will remain at the stage of intentions while not influencing policies. The paper also reflects on the discussions held during a peer review workshop organised in Riga on 23-24 February 2014 where four countries presented their RIS3 work on implementation and policy mix (Estonia, Latvia, the Czech Republic and England). The paper concludes underlining the challenges and the way forward in designing and implementing RIS3-oriented policy mixes.