Estimating peak river discharge, a critical issue in engineering hydrology, is essential for designing and managing hydraulic infrastructure such as dams and bridges. In the UK, practitioners typically apply the Flood Estimation Handbook (FEH) statistical method which estimates the design flood as the product of a relatively frequent flow estimate (the index flood, IF) and a regional growth factor. For gauged catchments the IF is estimated from observations. For ungauged catchments it is computed through a multiple regression model. While the FEH IF method provides peak flow estimates that are statistically robust, it does not readily take into account catchment heterogeneity or effect of environmental change on river flows. This study presents a new methodology to estimate the IF at national scale using continuous simulation from a physically based hydrological model (Grid-to-Grid). The methodology is tested across Great Britain and compares well with IF estimates at 550 gauging stations (R2 = 0.91). The promising results for Great Britain support the aspiration that continuous simulation from large-scale hydrological models coupled with increasing availability of global weather and climate products, could be used to estimate design floods in regions with limited gauge data or affected by environmental change.