To reduce energy consumption for space heating, a coordinated action on energy supply, building fabric and occupant behavior is required to realize sustainable improvements. A reduction in district heating supply temperature is an interesting option to allow the incorporation of renewable energy sources and reduce distribution losses, but its impact on the final users must be considered. This aspect is especially critical as most European countries feature an old building stock, with poor insulation and heating systems designed for high-temperature operation. In this study, a complete methodology is devised to evaluate the effect of district heating temperature reduction on the end users by modeling all the stages of the system, from the primary heat exchanger to the indoor environment. A dynamic energy performance engine, based on EN ISO 52016-1:2017 standard and completed with a heat exchanger model, is implemented, and its outputs are used to calculate thermal comfort indicators throughout the heating season. As a practical application, the method is used to evaluate different scenarios resulting from the reduction of primary supply temperature of a second-generation district heating network in Northern Italy. Several building typologies dating back to different periods are considered, in the conservative assumption of radiator heating. The results of the simulations show that the most severe discomfort situations are experienced in buildings built before 1990, but in recent buildings the amount of discomfort occurrences can be high because of the poor output of radiators when working at very low temperatures. Among the possible measures that could help the transition, actions on the primary side, on the installed power and on the building fabric are considered. The investigation method requires a limited amount of input data and is applicable to different scales, from the individual building to entire urban areas lined up for renovation.