SUMMARY The structure of the Himalayas in Nepal is characterized by underthrusting of the Indian lithosphere beneath the chain along the Main Himalayan Thrust (MHT). The MHT is affected by major earthquakes of M > 8 that have ruptured segments several hundred kilometres in length. The study of historical seismicity underlines the existence of a significant seismic gap between the 1905 Kangra and the 1934 Bihar‐Nepal earthquake areas in Western Nepal. This contribution presents a numerical model of the interseismic deformation using the ADELI 2-D finite-element code. A parametric study has been performed to estimate the influence of the topography, the geometry of the flat‐ramp‐flat transition of the MHT and its rheology. The results of these runs are compared along three cross-sections of Eastern, Central and Western Nepal using various recordings of the active deformation of Nepal (neotectonics, microseismicity, GPS velocities, vertical displacement rates deduced from comparative levellings). The results of this study suggest: (1) a small amount of aseismic slip along the southern part of the MHT and (2) an abrupt change in geometry of the MHT between Central and Western Nepal. The stress build-up in Eastern and Central Nepal is produced by coupling of a bend (flat‐ramp transition) of the MHT and a brittle‐ductile transition at the foot of the ramp. In Western Nepal, on the other hand, stress build-up is only induced by a brittle‐ductile transition located along the low-angle part of the MHT. This difference suggests the presence of a lateral ramp on the MHT to allow transition between the Central and Western Nepal geometries of the MHT. This change in MHT geometries between Central and Western Nepal is also clearly marked in the Himalayan relief: an abrupt decrease in altitude and incision between Central and Western Nepal.