We derive and validate a quadruple integral expression for calculating the diffraction loss in an isotropic propagation medium between circular ultrasonic transducers with time-harmonic radiation. The distinctive feature is the generic non-coaxial configuration with arbitrary transducer size and orientation. By performing several measurements, we validate the integral expression and we demonstrate that nowadays it is feasible to perform the required numerical integration to obtain the diffraction loss over an entire volumetric sound pressure field on a state-of-the-art personal computer with reasonable computation time on the order of a few minutes only. Excellent agreement between calculated results and experiments prove the approach and the generic nature of our expression ensures its wide and simple applicability for efficient diffraction loss calculations.