We study H=D^*D+V, where D is a first order elliptic differential operator actingon sections of a Hermitian vector bundle over a Riemannian manifold M, and V is a Hermitian bundle endomorphism. In the case when M is geodesically complete, we establish the essential self-adjointness of positive integer powers of H. In the case when M is not necessarily geodesically complete, we give a sufficient condition for the essential self-adjointness of H, expressed in terms of the behavior of V relative to the Cauchy boundary of M.