The importance of a measurement of power system inertia in the context of the continuing replacement of synchronous generators with renewable energy sources is considered. A detailed description of the frequency time-series associated with the power system response to the loss of a major source of power in-feed is discussed. The purpose of this is to identify what part of the response is operationally associated with inertia, such that it can be measured and subsequently used for grid control and planning. A novel reference method is proposed, in particular, a signal processing transform to decompose the frequency time-series in order to isolate the operational inertial response. Power system modeling of a major loss event on the GB grid is used to verify the method. A measurement campaign is described and measurements from 23 major infeed loss events in the GB grid are presented. Inertia results from the new method and associated uncertainties are compared with the electricity system operator's estimates for each loss event.