The regenerator is one of the key components in the liquid desiccant air-conditioning system, and improvement of the regenerator performance is key to promoting the overall system energy efficiency. This study entails the investigation of a vacuum multi-effect membrane distillation system (V-MEMD) for liquid desiccant regeneration. The V-MEMD regenerator possesses the merits of high energy efficiency and zero desiccant carry-over. A thermodynamic model has been developed to study the regeneration process based on the principles of heat and mass transfer and heat and mass balances. The model is validated with experimental data, and the discrepancies are observed to be within 10% and 5% for regeneration rate and brine concentration, respectively. Employing the developed and validated model, several V-MEMD configurations have been investigated and the effects of key operating parameters are evaluated. The regenerator performance is observed to degrade at higher feed concentrations, while a higher hot water temperature promotes regeneration rate and thermal efficiency. The proposed configurations expand the operation range of the V-MEMD regenerator to greater than 40 wt% under a heat source temperature of 70 degrees C. Compared with existing liquid desiccant regeneration systems, the specific energy consumption is reduced by 10-50%.