The purpose of this paper is to push forward the theory of operator-valued Riemann-Hilbert problems and demonstrate their effectiveness in respect to the implementation of a non-linear steepest descent method a la Deift-Zhou. In this paper, we demonstrate that the operator-valued Riemann-Hilbert problem arising in the characterization of so-called c-shifted integrable integral operators allows one to extract the large-x asymptotics of the Fredholm determinant associated with such operators.