One of the main factors impeding nuclear power plant (NPP) construction is their economics. In this study, a systematic differential economics evaluation approach was developed through the use of the Code of Accounts guidelines to assess the costs of nuclear power plants. The methodology, entirely based on publicly available data, may serve as a template to evaluate direct costs for reactors of any size and design at any stage of developments. In particular, this approach was used to assess the costs of the Integral Inherently Safe Light Water Reactor (I2S-LWR).The I2S-LWR is a design concept of a large (∼1000 MWe) light water reactor. One of its key design features promoting inherent safety is implementation of an integral primary circuit configuration, which however necessitates a compact design of the core and primary circuit components.Through the methodology here presented, a representative loop PWR design was taken as a reference and the differential cost was estimated for each individual account based on the design difference, or similarity. Cost scaling techniques were applied to the accounts representing systems that differ from the ones of the reference PWR. Cost estimating techniques were used to evaluate cost of innovative components that are not part of standard PWR designs. By evaluating the cost difference of the I2S-LWR from the standard PWR, rather than the absolute cost, the uncertainty in the estimate is reduced. A similar approach was used by ORNL to estimate the cost of a Fluoride-salt High-temperature Reactor (FHR).A traditional four-loop PWR plant with a core thermal power of 3417 MWth (1144 MWe) was selected as the reference. Costs for that plant were prepared in 1978 by the Department of Energy (DOE) Energy Economics Data Base (EEDB), averaging actual cost incurred in the construction of several nuclear power plants (NPP), itemized with a great level of detail according to the Code of Accounts. This best estimate costs are denoted PWR12-BE. For each account, the cost of equipment, site labor and site material is provided. Industry experts at Westinghouse Electric Company performed a “sanity check” of the cost items, adjusting the cost of several items to match the current market and supply chain data.The detailed cost assessment of I2S-LWR was performed, systematically analyzing cost for each account, and applying the differential economics approach. First, Relative importance of each account, i.e., its contribution to the total cost was established, to help focus analysis on the most significant contributors. Moreover, the accounts describing components that are different than that of the PWR12-BE were identified.The integral configuration of the reactor has important implications on the cost of the reactor plant equipment (accounts 22x). Turbine generator equipment (Accounts 23x) is not believed to be much different than that of the reference design. I2S-LWR structures (Accounts 21x) mainly differ from that of a standard LWR as several buildings (containment building, shield building, annex building, waste processing building, fuel storage building) are integrated into a single building (nuclear island). Yardwork has a higher cost for the I2S-LWR, as the NI is partially below grade. On the other hand, due to its compact Nuclear Island footprint, I2S-LWR facilitates (and includes in its reference version) the use of seismic isolators, which contribute to reducing the direct cost. The total capital investment cost (TCIC), on the $/kW basis, of I2S-LWR is 5.84% lower than that of PWR12-BE, in spite of the lower power output of I2S-LWR. However, for the Western US (0.7 g), benefits of the seismic isolation are more pronounced, and the I2S-LWR total capital investment cost is 13.02% lower than that of PWR12-BE. If the I2S-LWR is compared to a PWR10-BE (traditional loop design, but scaled to the same power level as I2S-LWR), the savings are even higher, in the range 11.12%–17.89%.The analysis indicates that I2S-LWR has potential to offer an economically attractive design, with TCIC lower than that of a nuclear power plant based on a traditional loop PWR design. In other words, I2S-LWR design offers significantly enhanced safety, while at the same time improving economics.The differential economics approach developed in this paper can be used in identifying changes in cost of key components in order to improve the economics of a nuclear reactor design. The method can also help compare the economics of advanced Generation IV reactors and innovative water-cooled SMR (Small Modular Reactors) with respect to standard LWR technologies. In summary, the differential economics approach and can be used as a tool capable of helping stakeholder decisions.