The Main-Sieg-Express is a Regional-Express service operated by the German states of North Rhine-Westphalia (NRW) and Hesse from Siegen via Gießen to Frankfurt.

On 25 June 2008, the Rhein-Main-Verkehrsverbund (Rhine-Main Transport Association, RMV) and the Zweckverband Nahverkehr Westfalen-Lippe (Local transport association of Westphalia-Lippe, NWL) announced in a joint press statement that Hessische Landesbahn has won a Europe-wide tender and would take over the operation of the service for 13 years with effect on 12 December 2010.

The Regional-Express operates from Siegen to Giessen as RE 99 on the Dill line stopping in Haiger, Dillenburg, Herborn and Wetzlar.

In Giessen, from Monday to Friday, it is coupled together with a set from Marburg, which is designated as RE 98, and reverses to run on the Main-Weser Railway to Frankfurt with a stop at Friedberg.

A service called RE-Sprinter is operated from Monday to Friday during the peaks in each direction, which runs on the Dutenhofen–Gießen-Bergwald route, which is otherwise used only by freight trains.