We present a comprehensive analysis of the wall-plug efficiency of mid-infrared (λ ∼ 4–10 μm) quantum cascade (QC) lasers, by taking into account the transition efficiency of the active region, the light out-coupling efficiency from the emission facet, the voltage efficiency across the superlattice, and the current efficiency including the leakage and thermal backfilling current densities at threshold. All relevant parameters including their interdependencies have been taken into account and analyzed in order to optimize the wall-plug efficiency of practical QC lasers. Expressions for optimizing the extraction energy Δinj and the mirror loss αm are deduced, which are then used to maximize the wall-plug efficiency of QC lasers. Finally, predictions for the wall-plug efficiency of realistic QC lasers are made both at room temperature and at low temperature. Good agreement is found with corresponding experimental data from the literature.