We prove the rationality and irreducibility of the moduli space of-what we call-the endomorphism-general instanton vector bundles of arbitrary rank on P 3 . In particular, we deduce the rationality of the moduli spaces of rank-2 mathematical instantons. This problem was first studied by Hartshorne, Hirschowitz-Narasimhan in the late 1970s, and it has been reiterated within the framework of the ICM 2018.