This paper presents a numerical analysis of a trigeneration system in a hospital, aiming at determining the cost-optimal operating strategy as a function of the energy demands to be matched. The system includes: A natural gas fired reciprocating engine, heat exchangers for waste-heat recovery, a single-stage LiBr-H 2 O Absorption Chiller (ACH), a cooling tower, pumps, a backup boiler, a backup vapour-compression electric chiller, storage tanks, valves, mixers. For such system, a dynamic simulation model was developed in TRNSYS environment; the model includes detailed algorithms for all the components of the system. A case study was developed, referred to a hospital application, in which a Combined Heat, Cooling and Power (CHCP) system provides electricity, thermal and cooling energy. The electric energy demand was obtained by using real measured data and calibrating hospital literature data, whereas the demand for heating and cooling was estimated by means of a detailed simulation model. A detailed economic analysis was also included in the model, aiming at investigating the optimal control strategy needed to maximize the overall thermo economic performance of the system. To this scope, different control strategies were analysed. The most conventional operating strategy, Thermal Load Tracking mode (TLT), was compared with two alternative strategies: The Maximum Power Thermal Load Tracking mode (MPTLT) and the Electricity Load Tracking mode (ELT). MPTLT is a strategy featured by a thermal load tracking mode, but the engine, differently from TLT one, operates always at maximum power. ELT is a strategy in which the power provided by the engine is always less or equal to the electrical demand. In the paper, the results of the case study are presented on different time bases (days, weeks, years). Such results show that the ELT control strategy can achieve a better profitability, with a simple pay-back period, SPB, equal to 4 years. The conventional strategy (TLT) is shown to be the worst from the economic point of view, but among the best as for energy saving potential.