The Roer Valley Rift System (RVRS) is located between the West European rift and the North Sea rift system. During the Cenozoic, the RVRS was characterized by several periods of subsidence and inversion, which are linked to the evolution of the adjacent rift systems. Combination of subsidence analysis and results from the analysis of thickness distributions and fault systems allows the determination of the Cenozoic evolution and quantification of the subsidence. During the Early Paleocene, the RVRS was inverted (Laramide phase). The backstripping method shows that the RVRS was subsequently mainly affected by two periods of subsidence, during the Late Paleocene and the Oligocene–Quaternary time intervals, separated by an inversion phase during the Late Eocene. During the Oligocene and Miocene periods, the thickness of the sediments and the distribution of the active faults reveal a radical rotation of the direction of extension by about 70–80j (counter clockwise). Integration of these results at a European scale indicates that the Late Paleocene subsidence was related to the evolution of the North Sea basins, whereas the Oligocene–Quaternary subsidence is connected to the West European rift evolution. The distribution of the inverted provinces also shows that the Early Paleocene inversion (Laramide phase) has affected the whole European crust, whereas the Late Eocene inversion was restricted to the southern North Sea basins and the Channel area. Finally, comparison of these deformations in the European crust with the evolution of the Alpine chain suggests that the formation of the Alps has controlled the evolution of the European crust since the beginning of the Cenozoic.