Generation IV high-temperature-reactor (HTR) systems use closed gas Brayton cycles to realize high thermal efficiency in the range of from 40% to 50% or more. The waste heat is removed through coolers by water at a substantially greater average temperature than in conventional condensing Rankine steam cycles. This paper introduces an innovative advanced multieffect distillation (AMED) design that can enable the production of substantial quantities of low-cost desalinated water using waste heat from closed gas Brayton cycles. A reference AMED design configuration, optimization models, and simplified economics analysis are presented. By using an AMED distillation system, one can fully utilize the waste heat from closed gas Brayton cycles to desalinate brackish water and seawater without affecting the cycle thermal efficiency. Analysis shows that cogeneration of electricity and desalinated water can increase net revenues for several Brayton cycles while generating large quantities of potable water. AMED combined with closed gas Brayton cycles could significantly improve the sustainability and economics of Generation IV HTRs.