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• A mathematical model to predict the aerogel blanket's effective thermal conductivity at the material scale is developed considering the gaseous, radiative, and solid heat transfer. • The in-situ thermal performance of the aerogel-based blankets is estimated via a real-scale experimental test facility using the average method as well as using two dynamic statistical methods. • The annual energy performance and economic analysis of a single-family detached house with and without the aerogel-based blanket is examined for different climate. Composite materials made of silica aerogel in a fibrous inorganic mat, hereafter called "aerogel blankets", represent promising insulating materials that can overcome the low mechanical resistance of monolithic aerogels, while preserving their very low thermal conductivity. Firstly, this paper details an experimentally validated mathematical model to predict the aerogel blankets' effective thermal conductivity, as a function of the blankets' density, fiber volume fraction, and temperature. Secondly, an experimental test building retrofitted internally with a layer of needle glass fiber (NGF) aerogel blanket is monitored, and its thermal behavior is compared to the baseline case before the retrofit. The retrofitted wall U-value is derived from experimental data series using stationary and transient parametric methods. Then, a validated whole building Energy Plus numerical model is used to predict the annual energy consumption of a detached single-family house retrofitted with an NGF aerogel blanket, in the climates of Brussels (Belgium), Nice (France), and Stockholm (Sweden). Lastly, a 1-D COMSOL multiphysics model evaluates the economic profitability of installing the blanket as an interior thermal insulation system. Results show that the aerogel blankets have an effective thermal conductivity of about 0.0165 W.m−1.K−1. The designed mathematical model can reliably predict the gaseous conduction in the blanket, but deviations from the experimental measurements appear when considering the radiative and solid conduction components. The blanket's effective thermal conductivity increases with fiber volume fraction and temperature while its dependency curve to density is concave, with a minimum for densities of around 140 kg.m−3. Retrofitting a wall with 2.5 cm of NGF aerogel blanket as an internal insulation system almost doubles the thermal resistance of the experimental wall and decreases the heating load by more than 40 % in all tested climates. Internal thermal insulation with aerogel blankets is more profitable than conventional insulation materials, in places of high floor area price, because it can preserve the indoor living space. [ABSTRACT FROM AUTHOR]