We prove the differentiability of Lipschitz maps X → V, where X denotes a PI space, i.e. a complete metric measure space satisfying a doubling condition and a Poincaré inequality, and V denotes a Banach space with the Radon–Nikodym Property (RNP). As a consequence, we obtain a bi-Lipschitz nonembedding theorem for RNP targets. The differentiation theorem depends on a new specification of the differentiable structure for PI spaces involving directional derivatives in the direction of velocity vectors to rectifiable curves. We give two different proofs of this, the second of which relies on a new characterization of the minimal upper gradient. There are strong implications for the infinitesimal structure of PI spaces which will be discussed elsewhere.