Design and safety assessments of geological disposals of heat-emitting radioactive waste require accurate evaluation of the thermal conductivity of the host medium. This paper presents a new approach to evaluate the anisotropic thermal conductivity of Boom Clay, a clayey layer that is studied as a potential host medium in Belgium by ONDRAF/NIRAS. The present approach is based on an inverse analysis of two in situ heater tests (the small-scale ATLAS IV Heater test and the large-scale PRACLAY Heater test) carried out in the HADES underground research facility (URF). The inverse analysis is performed by using the absolute error function and tolerant error-based method based on temperatures measured from 60 sensors across the two tests (i.e., from 29 sensors during the 900-day heating and cooling phase in the ATLAS IV Heater test and from 31 sensors during the nearly 7-year heating phase in the PRACLAY Heater test). In addition, thousands of numerical modeling cases are applied for both tests. The objective is to estimate a reasonable range of thermal conductivity variation that is characteristic of the entire host clay. Finally, a thermal conductivity range (λh, λv) = (1.55–1.95, 1.10–1.25) W/(m⋅K) is identified for the Boom Clay.