42 high speed trains travel on the Rhine-Rhône High Speed Line daily – 12 on the North-South route and 30 on the East-West route. International services are offered to Frankfurt and the Rhine Valley from Marseille, to Zürich and Basel from Paris, and to Luxembourg from Montpellier and Marseille. These services stop at various stations en route allowing access to international destinations from Lyon, Dijon, Besançon, Belfort-Montbéliard and Mulhouse.

Fast and frequent connections are proposed between the stations along the line from Dijon through to Mulhouse with up to 11 daily return trips. There are 5 daily return services between Strasbourg and Lyon with stops at intermediate stations, although the express service with a travel time of under 3h10 between the two cities ceased to be offered in 2019. The new high speed stations of Besançon Franche-Comté TGV and Belfort-Montbéliard TGV are connected to the nearby city centres by shuttle train or  bus services, and by regional train to the Jura canton in Switzerland in the case of Belfort-Montbéliard TGV.