Since many years ago, multilateration has been used in precision engineering notably in machine tool and coordinate measuring machine calibration. This technique needs, first, the use of laser trackers or tracking interferometers, and second, the use of nonlinear optimization algorithms to determine point coordinates. Research works have shown the influence of the experimental configuration on measure precision in multilateration. However, the impact of floating-point precision in computations on large-scale multilateration precision has not been addressed. In this work, the effects of numerical errors (rounding and cancellation effects) due to floating-point precision (number of digits) were studied. In order to evaluate these effects in large-scale multilateration, a multilateration measurement system was simulated. This protocol is illustrated with a case study where large distances (≤20 m) between pairs of target points were simulated. The results show that the use of multi-precision libraries is recommended to control the propagation of uncertainties during the multilateration computation.