Heating, ventilation, and air-conditioning (HVAC) systems play a key role in providing healthy, productive, and thermally comfortable built environment for the occupants. Improper HVAC design will degrade occupants’ satisfaction with the built environment, potentially affecting their performance which can be valued up to 200 times the building’s energy costs. In the top two energy consuming countries, the US and China, over 40% of the energy use in buildings with HVAC systems can be attributed to those systems. Moreover, 13% of total greenhouse gas emissions in the US can also be ascribed to HVAC systems. On a global scale, electricity demand for space cooling could increase by up to 210% by 2050 from 2016 levels. This rapid growth prediction is driven by the fact that most of the world’s population and wealth growth is happening in the tropics and in middle-income countries where air-conditioning has relatively small penetration in buildings. There are serious implications to electrical grid systems and most importantly, to our ecosystems if HVAC design is left unchecked.Therefore, in this dissertation we investigate high thermal mass radiant systems (HTMR) as a promising strategy to address the challenges and strain imposed by HVAC systems, with the focus on space cooling. HTMR, and other radiant systems in general, deliver 50% or more of the design heat transfer through thermal radiation, have large heat transfer areas, and have high heat transport efficiency. The “high thermal mass” in HTMR comes from the fact that there is a significant time delay, measured in hours, between a control action and the temperature response observed in the zone as a result of the thermal inertia in the concrete. This property has presented obstacles to the adoption rate of HTMR in the building stock in the US. In general, building designers are unfamiliar with how to design and control HTMR without adversely affecting occupants’ thermal satisfaction while also balancing other performance objectives such as capital and operational costs. Yet, because of the thermal response delay property, HTMR presents building designers and other stakeholders with innovative and beneficial design and control options that are difficult to implement in the more typical all-air systems to reduce equipment and electricity costs while maintaining acceptable indoor temperatures.The development of most building standards, guidelines, and tools have focused on all-air HVAC systems. One example is the standard design procedure for sizing cooling systems. The standard design procedure includes a definition of space cooling load which serves as the basis to size HVAC components from the zone level to the central cooling plant. However, that space cooling load definition is too narrowly constrained and omits fundamental principles that are essential to the operation of various cooling systems, including HTMR. We provide a critical review of the standard design procedure for sizing cooling systems to identify fundamental flaws, explain how it has influenced building energy modeling, system sizing and operation in practice, and propose a new definition for space cooling load along with an associated cooling system design procedure that better suits a variety of systems and control strategies. We conduct whole building energy simulations with the focus on HTMR to demonstrate the consequences of the standard procedure and compare it to our recommended procedure. The results show that following the standard design approach for HTMR can lead designers to underestimate the peak space cooling load by 100%, yet also select cooling plant equipment that is 100% larger than necessary due to its large thermal inertia. The standard design obscures considerable opportunities to reduce costs and improve energy efficiency and thermal comfort.For example, large heat transfer areas allow HTMR to take advantage of high-temperature cooling, i.e. using higher than typical supply water temperature to perform space cooling, and potentially eliminating the use of the vapor-compression refrigeration cycle. In lieu of this energy- and cost-intensive cycle, more sustainable cooling plants that use adiabatic cooling with cooling towers or fluid coolers can provide cool water production for HTMR. We used whole building energy simulation to determine the warmest supply water temperature that is able to still maintain comfortable temperatures for various building, HTMR, and control strategy designs. We used single zone models that represent ASHRAE 90.1-2016 and Title 24-2016 code-compliant buildings in 14 US and 16 Californian representative climates during the climates’ cooling design day. We found the warmest supply water temperature to be 18.2, 21.4, 23.4 °C for the first quartile, median, and third quartile, respectively, among all test cases. Cooling towers can generate these required supply water temperatures during nighttime periods when their performance is at their highest. There is great potential to avoid installing a compressor-based refrigeration system in most climates, while only a few will require more than code-compliant designed buildings.A key determinant to the successful implementation of HTMR is the control system. Improved HVAC control can improve energy, cost, and thermal comfort performance over typical control strategies, but improper control and faults can penalize them on a similar scale. We developed and experimentally tested a new HTMR control strategy that independently adapts to each radiant zone’s observed indoor temperatures in two California buildings located in distinct, contrasting climates. The results show that the new HTMR control strategy reduces the number of hours that zone dry-bulb temperatures exceed predefined thermal comfort limits from 9.1% to 1.6% as a proportion of total occupied hours when compared to the buildings’ existingcontrols. We verified that the new control strategy did not have adverse effects on occupant thermal comfort satisfaction through a detailed “right-now” satisfaction survey. The new strategy also reduces the number of average daily minutes HTMR manifold valves open for water flow through the slab, a proxy for energy consumption, by up to 93%.Finally, we created an interactive web-based tool for the early design of HTMR. The primary aim of this design tool is to provide an interface for estimating the performance of HTMR under steady-state and transient conditions. It allows users to estimate the impact of innovative control strategies such as nighttime pre-cooling on indoor temperature response. The tool website not only contains resources and lessons learned through the investigations presented in this dissertation but also from the overarching investigations on radiant systems undertaken by the Center for the Built Environment, which this Ph.D. study was part of.In this dissertation, we contributed on revising the fundamental cooling load definition and associated design procedure for applicability to a broader range of systems and applications, demonstrated the potential of using HTMR coupled with more sustainable cooling plants in a diverse set of US climate zones, developed and tested adaptive control strategies that take advantage of HTMR’s high thermal inertia to shift the building’s cooling load to more beneficial periods, and facilitate mechanical designers’ decision making with respect to HTMR systems through our early design web-based tool. These innovations will help achieve reductions in energy and greenhouse gas emissions attributed to HVAC systems and therefore support our global shift towards a more sustainable built environment.