Semi-active primary suspensions are an effective means of improving ride quality in high-speed railway vehicles in relation to the mitigation of car-body bending vibration. In this paper, prototype magnetorheological (MR) dampers are tested and the results are used to define a mathematical model of the dampers. Then, three control schemes for semi-active primary suspensions are proposed: Skyhook, LQG and Mix-1-Sensor, and their performance is assessed by means of Hardware-In-the-Loop (HIL) tests considering a simple quarter-vehicle model which is run on a real-time board and set in interaction with one physical MR damper. The results show that all three considered control strategies lead to a reduction of car-body vibration by around 30% and a very good agreement is found between HIL tests and numerical simulations in which the physical damper is replaced by the mathematical damper model. The damper model is finally interfaced with a flexible multi-body model of the complete vehicle to provide further assessment of semi-active control. The results of the latter simulations show that the semi-active suspension could provide an improvement of the (Formula presented.) ride quality index in the order of 40–45% with respect to the passive vehicle for all three control schemes.