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Efficiently leveraging new sources of flexibility is critical to mitigating load balancing challenges posed by variable renewable resources. The thermal inertia of commercial buildings allows us to shift their power consumption on minute to hourly timescales to provide demand response to the grid while maintaining occupant comfort. Global thermostat adjustment (GTA) provides a readily available and scalable approach for implementing load shifting demand response using commercial heating, ventilation, and air conditioning (HVAC) systems, since it leverages the inherent sophistication of modern building automation systems. However, there is an incomplete understanding of GTA’s performance for this purpose and its impact on building systems and occupant comfort. In this paper, we explore the performance of GTA by analyzing results from nearly nine hundred experiments on eight university campus buildings in Michigan and North Carolina. Using GTA, we manipulate each building’s thermostat setpoints causing the building to shift its power consumption with respect to its baseline. We quantify the magnitude of HVAC power response, energy use of HVAC subsystems, and impact on occupant comfort. Finally, we connect our experimental results with power system operation using an optimization model that coordinates GTA actions across a large collection of grid-interactive efficient buildings (GEBs) to reduce high ramp rates on the grid and mitigate renewable energy curtailment. Overall, our work finds that the impacts on HVAC subsystems are often complex, and may result in additional energy being consumed by fans and terminal reheat. These effects must be considered when using GTA for load shifting. Additionally, we demonstrate that occupant comfort, as assessed by indoor temperature and humidity, can be maintained during GTA events. From a societal perspective, our modeling work finds that the additional renewable energy that can be integrated through the use of GTA strategies eclipses any additional energy consumed by buildings.