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• Effects of multi-zone heating systems in residential buildings are assessed. • Data obtained from 336 scenarios in Mediterranean climates are evaluated. • Results are evaluated under economic and energy criteria. This paper explores the effects of multi-zone heating systems in residential buildings in different Mediterranean climates. The aim is to evaluate their potential in residential sectors to provide a general basis from the results (from the energy and economic point of view). In addition, if feasible, a further detailed evaluation of this management strategy for optimising the energy use in residential buildings would also be carried out. To do so, the effects of two different zoning controls in different types of apartment, occupancy patterns, building characteristics and locations in Spain, have been assessed. Different combinations of these parameters have resulted in 336 different scenarios that have been dynamically simulated using Design Builder software. The obtained energy results have been analysed in detail. Moreover, an economic analysis of these results has also been carried out to evaluate the economic feasibility of these systems in residential buildings located in temperate climates. This has been calculated by evaluating the maximum investment that can be assumed in each scenario to achieve different payback periods (namely 10 and 20 years). The results obtained show that these systems could be a cost-effective strategy aimed at reducing the energy consumption in residential buildings, not only in cold climates, such as is shown in the literature (the majority of the studies found are located in the UK and northern countries), but also in more temperate climates, such as that of Spain. Savings of around 20% were obtained in the most usual scenarios in Spain (coherent with results obtained in previous studies in the UK found in the literature), showing that in several cases, the initial investment in zone-controlled systems could be paid off in less than ten years, especially in large apartments and the coldest weather conditions. [ABSTRACT FROM AUTHOR]