The comparative analysis of means of control of a thermal mode at minimization of a complex of the basic parameters in various combinations with indicators of reliability and dynamics of functioning of one-stage thermoelectric cooler is resulted. The study was conducted for the operating range of temperature differences, standard heat load and different geometry of the branches of thermocouples. According to the results of research to minimize the sets of basic parameters in interaction with the indicators of reliability and dynamics of work, a number of current modes of operation have been developed. The developed mathematical models for the optimal operating current from the relative temperature difference and heat transfer of the radiator for the proposed operating modes are analyzed. The results of calculations of the main parameters, reliability indicators, and time of transition to stationary mode of operation for different current modes of operation in the range of temperature differences for different geometry of branches of thermoelements are given. The extremes of dependences of the cooling coefficient, heat dissipation capacity of the radiator, the amount of energy consumed on the relative operating current are determined, which is essential for the implementation of the control function. The possibility of choosing the current mode of operation for optimal control of the thermal regime of single-stage thermoelectric devices manufactured by the same technology, taking into account mass, size, energy, reliability and dynamic characteristics. The developed method of optimal regulation of the thermal regime of a single-stage thermoelectric cooler based on minimizing the set of basic parameters allows finding and choosing compromise solutions taking into account the importance of each of the limiting factors.