This paper presents an analysis of a possible energy retrofit of an existing University Hospital District, located in Naples (Italy), by using an innovative renewable polygeneration system. This system integrates both Concentrating PhotoVoltaic/Thermal collectors (CPVT) and Solar Heating and Cooling (SHC) technologies. The CPVT parabolic trough collectors are equipped with triple-junction PhotoVoltaic (PV) cells: this technology usually shows ultra-high energy conversion efficiencies. The main components of the system are: CPVT collectors, a single-stage LiBr–H2O absorption chiller, storage tanks and balance of plant devices. The system is assumed to be installed at a University Hospital District located in Naples (Italy), equipped with a gas-turbine cogeneration system. The data regarding cooling, heating and electrical demands and productions are measured for a one-year operation. The CPVT produces electrical energy, which is consumed in part by the system parasitic loads, whereas the eventual surplus is fed in the electrical grid. Simultaneously, the CPVT provides heat, used for space heating, for domestic hot water and/or to drive the absorption chiller, which produces cooling energy. The system is designed and dynamically simulated in TRNSYS environment, including detailed and validated mathematical models for the simulation of all the components. The results are analysed from both energy and economic points of views, using parametric analyses and thermo-economic optimizations. The energy performance of the system is excellent since all electrical and thermal energies produced by the renewable system are consumed by the user. The economic results show that the system can be profitable (pay-back period around 12 years) even without any public funding. In case of feed-in tariffs, the system becomes extremely profitable from the economic point of view. The thermo-economic optimization, based on a mixed heuristic/deterministic algorithm, shows that the system profitability can be further improved, increasing solar field area and decreasing storage specific volumes for m2 of collectors installed.