This paper is devoted to the philosophy of Henricus Regius, a Dutch philosopher and one of the first followers of René Descartes. Regius’ philosophy presents an original version of Cartesianism insofar as it relies on a certain number of Cartesian principles and on many particular Cartesian explanations in natural philosophy, while at the same time rejecting Descartes’ metaphysics. Regius’ empiricist theory of knowledge is precisely intended to replace Descartes’ metaphysics. I first explore this original empiricist theory by relying on a systematic comparison of the three editions of Regius’ main work. The expression of this empiricism becomes more and more radical and goes hand in hand with a limited skepticism. I show that it leads Regius to a new conception of vision that, although close to that of Descartes, has to account for the visual perception of the geometrical and spatial properties of objects without any innate ideas. Then I present the consequences of Regius’ empiricist theory of knowledge on the way the principles of natural philosophy can be grasped and on the role that can be attributed to experience in the explanation of natural phenomena.