Chilled-water plants with multiple chillers account for a significant fraction of energy use in large commercial buildings. Real-time optimization and sequencing of such plants is thus critical for building energy efficiency. Due to the cost and complexity associated with calibrating a chiller plant model to field operation, model-free control has become an attractive solution. Recently, Mu et al. (2015) proposed a model-free real-time optimization and sequencing strategy based on extremum seeking control (ESC) for chilled-water plants with multiple parallel chillers. In this ESC scheme, the variable to be optimized is the total power from the chiller compressors, cooling tower fans, condenser and evaporator loop water pumps, while the manipulated inputs include the tower fan airflow, condenser water flows and evaporator leaving chilled-water temperature setpoint. Two schemes are proposed for chiller sequencing: A) A chiller is turned on based on the measurement of chilled water valve position and is turned off when a chiller compressor is running at its nominal minimum speed. B) A chiller is turned on and off based on the measurement of operating cooling load. For Scheme A, Mu (2015) performed a comprehensive case study, and the simulation results demonstrated that the proposed framework performed well under various ambient, load and equipment conditions. However, for Scheme B, only one case was simulated. Although the two chiller sequencing schemes have a shared physical process in terms of chiller plant operation, it is necessary to evaluate the load-based Scheme B in terms of energy efficiency performance. This paper aims to provide a comprehensive evaluation for the Scheme B-based optimization and sequencing strategy for a multi-chiller chilled-water plant. Three ambient conditions are considered: i) 27 °C and 60%RH (Mild), ii) 37°C and 30%RH (Dry Hot), and iii) 37 °C and 80%RH (Humid Hot). For each of these ambient conditions, simulations are performed for the scenarios listed below, Scenario #3 is simulated with dynamic ambient and load profiles. Scenario #1. Two-chiller ESC with no sequencing under fixed ambient conditions Scenario #2. Chiller sequencing under variable load and fixed ambient conditions Scenario #3. Chiller sequencing with realistic ambient and load profile Scenario #4. Penalty Function based ESC Chiller Sequencing Scenario #5. ESC for Efficiency Recovery: Chiller A properly charged and Chiller B with a low refrigerant charge Scenario #6. ESC for Efficiency Recovery: Chiller A with nominal operation and Chiller B with heat exchanger fouling References B. Mu, Y. Li, T.I. Salsbury, J.M. House, Extremum Seeking Based Control Strategy for a Chilled-Water Plant with Parallel Chillers, ASME Dynamic Systems and Control Conference, Columbus, OH, paper no. 9949, 10 pages, 2015 B. Mu, Self-optimizing Control for Building Ventilation and Air Conditioning Systems,Ph.D.Dissertation, Department of Electrical Engineering, University of Texas at Dallas, December 2015