Vector-Like Quarks (VLQs) are predicted by several theoretical scenarios of new physics and, having colour quantum numbers, can copiously be produced at the Large Hadron Collider (LHC), so long that their mass is in the testable kinematic regime of such a machine. While it would be convenient to assume that such objects are narrow and can be treated in the so-called Narrow Width Approximation (NWA), this is not always possible, owing to the fact that couplings and particle content of such new physics scenarios are not generally constrained, so that a large value of the former and/or a large variety of VLQ decay channels into the latter can contribute to generate a large decay width for such extra quarks. We have addressed here the issue of how best to tackle in LHC analysis the presence of large (and model-dependent) interference effects between different VLQ production and decay channels as well as between these and the corresponding irreducible background. We have confined ourselves to the case of single production of VLQs, which is rapidly becoming a channel of choice in experimental searches owing to the ever increasing limits on their mass, in turn depleting the yield of the historically well-established double production channel. Indeed, this poses a further challenge, as the former is model-dependent while the latter is essentially not. Despite these conditions, we show here that an efficient approach is possible, which retains to a large extent a degree of model independence in phenomenological studies of such VLQ dynamics at the LHC.