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This study provides insights into the feasibility of a desiccant dehumidification-based Maisotsenko cycle evaporative cooling (M-DAC) system for greenhouse air-conditioning application. Conventional cooling techniques include direct evaporative cooling, refrigeration systems, and passive/active ventilation. which are commonly used in Pakistan; however, they are either not feasible due to their energy cost, or they cannot efficiently provide an optimum microclimate depending on the regions, the growing seasons, and the crop being cultivated. The M-DAC system was therefore proposed and evaluated as an alternative solution for air conditioning to achieve optimum levels of vapor pressure deficit (VPD) for greenhouse crop production. The objective of this study was to investigate the thermodynamic performance of the proposed system from the viewpoints of the temperature gradient, relative humidity level, VPD, and dehumidification gradient. Results showed that the standalone desiccant air-conditioning (DAC) system created maximum dehumidification gradient (i.e., 16.8 g/kg) and maximum temperature gradient (i.e., 8.4 °C) at 24.3 g/kg and 38.6 °C ambient air conditions, respectively. The DAC coupled with a heat exchanger (DAC+HX) created a temperature gradient nearly equal to ambient air conditions, which is not in the optimal range for greenhouse growing conditions. Analysis of the M-DAC system showed that a maximum air temperature gradient, i.e., 21.9 °C at 39.2 °C ambient air condition, can be achieved, and is considered optimal for most greenhouse crops. Results were validated with two microclimate models (OptDeg and Cft) by taking into account the optimality of VPD at different growth stages of tomato plants. This study suggests that the M-DAC system is a feasible method to be considered as an efficient solution for greenhouse air-conditioning under the climate conditions of Multan (Pakistan). [ABSTRACT FROM AUTHOR]