The S45 is the only S-Bahn route to operate entirely within Viennese city limits, and it is the most frequently operated single S-Bahn service, with intervals of 10 minutes during weekdays and 15 minutes during weekends and holidays.

It terminates at Handelskai (on the Stammstrecke) and also crosses the U6 there, the U3 at Ottakring and joins both ends of the U4 at Heiligenstadt and Hütteldorf.

Due to the short platform lengths, only single 4024s (Talent EMUs) and 4020s can operate on the route.

In the following years the line was renovated, expanded to two tracks and electrified with 15 kV 16,7 Hz.

Passenger traffic greatly increased when service was extended past Heiligenstadt to Handelskai in 1996, offering a connection to the Vienna Trunk Line and increased even more when the U3 U-Bahn line was extended to Ottakring.