In the design process of a cryogenic distillation plant for the separation of hydrogen isotopes, two main objectives, often impossible to achieve simultaneously, are taken into account: a high separation factor for different mixtures and isotope concentrations and the reduction of design, manufacturing, and operating costs with increased efficiency and safety. All this should result from the use of a method for calculating the separation efficiency, a method that will generate a conceptual design that must form the basis of the final technical design. Unfortunately, most design methods treat these plants as chemical plants, although in the case of cryogenic plants, it is not possible to readjust the new process operating parameters quickly and with great precision so that the separation efficiency and performance are not affected. There are three causes affecting the separation performance of cryogenic distillation plants, namely, nonideality of the cryogenic process, imperfection of heat exchangers, and heat losses. This paper presents our proposed solutions for increasing the efficiency of the cryogenic distillation process and discusses solutions tested in experimental campaigns with the cryogenic distillation stand developed in the Cryogenic Laboratory at ICSI Rm. Vâlcea.