Large-eddy simulations (LES) coupled to a model that simulates methane emissions from oil and gas production facilities are used to generate realistic distributions of meteorological variables and methane concentrations. These are sampled to obtain simulated observations used to develop and evaluate source term estimation (STE) methods. A widely used EPA STE method (OTM33A) is found to provide emission estimates with little bias when averaged over six time periods and seven well pads. Sixty-four percent of the emissions estimated with OTM33A are within ±30% of the simulated emissions, showing a slightly larger spread than the 72% found previously using controlled release experiments. A newly developed method adopts the OTM33A sampling strategy and uses a variational or a stochastic STE approach coupled to an LES to obtain a better fit to the sampled meteorological conditions and to account for multiple sources within the well pad. This method can considerably reduce the spread of the emissions estimates compared to OTM33A (92-95% within ±30% percent error), but it is associated with a substantial increase in computational cost due to the LES. It thus provides an alternative when the additional costs can be afforded to obtain more precise emission estimates.