This work addresses the problem of optimal design of trigeneration plants and discusses the factors that affect the operation and the feasibility of investment. The effect of various operation parameters and energy tariffs structures are studied and the performance of a trigeneration plant is presented and evaluated versus the investment size. A new operation strategy is being introduced and examined along with three existing strategies. The results incorporate various economical and performance indices that characterize the system, with reference to a case of a commercial hospital building.