To improve engine power at high altitude, the regulated two-stage turbocharger (RTST) which was applied to different altitudes was developed by the authors. The working process model of heavy-duty common-rail diesel engine matched with RTST was built to study the regulating characteristic of variable geometry turbocharger (VGT) vane and both turbine bypass valves and also matching performance of RTST with engine at different altitudes. The control scheme of RTST at different altitudes and engine operating conditions was first put forward, and the optimal opening maps of VGT vane and both turbine bypass valves at different altitudes and engine operating conditions were obtained. The results show that the optimal openings of VGT vane and both turbine bypass valves decrease with increase of altitude, and the optimal opening range of VGT vane becomes narrower with increase of altitude. The operating points of both high-pressure (HP) and low-pressure (LP) compressors locate at high-efficiency region of each compressor map, respectively, and compressor efficiency exceeds 70% at altitude of 5500 m. The total boost pressure ratio increases with altitude and reaches the maximum value of 5.1 at altitude of 5500 m. Compared with single-stage turbocharged engine, the rated power, maximum torque, and torques at lower engine speed at altitude of 5500 m increase by 48.2%, 51%, and 65–121% separately, and the minimum fuel consumption decreases by 12.6%.