In this paper, we study harmonic analysis on the affine Poincaré group P aff , which is a non-unimodular group, and obtain pseudo-differential operators with operator valued symbols. More precisely, we study the boundedness properties of pseudo-differential operators on P aff . We also provide a necessary and sufficient condition on the operatorvalued symbols such that the corresponding pseudo-differential operators are in the class of Hilbert-Schmidt operators. Consequently, we obtain a characterization of the trace class pseudo-differential operators on the Poincaré affine group P aff , and provide a trace formula for these trace class operators. Finally, we study the Wigner transform, and Weyl transform associated with the operator valued symbol on the Poincaré affine group P aff .