Abstract The optimization of design and operation of combined heat, cooling and power systems usually leads to select different plant lay-outs and size of components, depending on the adopted optimization criterion (maximum profit or energy saving or minimum environmental impact). This occurs when the current energy prices and the normative provisions supporting cogeneration are not able to coincide with the specific customer’s interest and the overall “social interest” for a reduction in energy consumption and in pollutants’ emissions. At EU level, polygeneration is considered to have a large potential for residential and commercial buildings district network, for the tertiary sector and for industrial applications. In such applications, it is often convenient to integrate the trigeneration system with a reversible heat pump, because of a low ratio between electric demand and that for heating and cooling. In this paper, the design and operation of such hybrid systems is discussed. The results achievable through different operation modes are compared and, with reference to a 600-rooms hotel and a 300-beds hospital in Italy, the effects on plant design from an hour-by-hour optimization of plant operation are assessed. Finally, the need for a flexible support system for cogeneration plants is put into evidence and some criteria are listed for an effective regulation.