The three-hour route took players through the city's best locations for catching Pokemon late Thursday, and the tram went at a particularly slow speed to allow the players' Pokemon eggs to hatch.
City authorities had to close off one bridge in the western German city and portable toilets were set up for the players, Die Welt newspaper reported.
"We have never had this much interest in a campaign - it's completely mad," said a spokesman for the tram operator Rheinbahn, which came up with the concept as a marketing tool and charged 8 euros (9 dollars)per ticket for Thursday's event.
The spokesman added that the Pokemon tram may become a regular event "if the hype remains."
- DPA