Abstract. A 4D rotation can be decomposed into a left-and a rightisoclinic rotation. This decomposition, known as Cayley's factorization of 4D rotations, can be performed using Elfrinkhof-Rosen method. In this paper, we present a more straightforward alternative approach using the corresponding orthogonal subspaces, for which orthogonal bases can be defined. This yields easy formulations, both in the space of 4×4 real orthogonal matrices representing 4D rotations and in the Clifford algebra C4,0,0.Cayley's factorization has many important applications. It can be used to easily transform rotations represented using matrix algebra to different Clifford algebras. As a practical application of the proposed method, it is shown how Cayley's factorization can be used to efficiently compute the screw parameters of 3D rigid-body transformations.Mathematics Subject Classification (2010). Primary 99Z99; Secondary 15A66.