In order to search for new desalination technologies to meet the growing water needs, this paper presents a parametric study of a novel, high-vacuum multiple-effect desalination system with barometric ejector-condensation activated with solar thermal energy, to demonstrate its technical feasibility. Aspen Plus simulation software was used for the parametric study, which was validated with the results reported in the literature. The high-vacuum multiple-effect distillation system has 14 effects, Top Brine Temperature of 68 °C and produces 96,033.6 L/d of water. The increase in the range of the pressure cascade (28.6–0.8 kPa), as well as of the temperature (68–4 °C), increases the capacity and efficiency of the desalination system. This is possible due to the implementation of an ejector that pumps, drags, and compresses vapor at 4 °C from the last effect of the system in order to condense it. In comparison to a conventional multiple-effect distillation, the Gain Output Ratio increases in 34.1 % because 25.4 % less energy from the generator is consumed. Furthermore, the system has a Recovery Ratio of 0.83, which corresponds approximately to a 120 % increase. Hence, the proposed desalination system significantly increases the potentiality of multiple-effect distillation systems. •A new MED system configuration that operates at high-vacuum;•A barometric ejector-condensation process is proposed to condense the vapor at 4 °C;•New operating conditions, which increase the efficiency of the system, are set;•The maximum sea-water pre-heating level is reached using less pre-heaters;•A variable-flow pump is used in order to ensure the proper functioning of ejector.