The six-mile stretch is closing for the 2012 Presidential Debate at the University of Denver.
The people who are in charge of making sure the traffic bump goes smoothly are part of Denver's Transportation Management Center.
"We're just trying to make sure people can get to where they need to go as efficiently as possible," Matt Wager, Director of Operations for Denver's Traffic Engineering Services, said.
The department monitors more than 300 of its own cameras set up around Denver's major roadways, as well as an additional 300 that are operated by the Colorado Department of Transportation.
On a scale of 1 to 10, the department says Wednesday's traffic problem will hover around a 6 or a 7.
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To help ease driver's concerns, they're going to increase signal times on both stretches of Santa Fe and Hampden by making sure the green lights stay green longer.
"We're going to keep traffic moving as fast as we can," Wager said.
Alternate routes have been shared with ambulance crews to make sure they can move through the traffic turmoil.
Some Tech Center businesses are adjusting work schedules around the traffic situation.
DISH Network's national headquarters in Englewood has more than 1,000 employees. A spokesperson says some employees will leave work early, some will work from home.
Your best bet, according to Wager, is to avoid the area all together between 5 p.m. and 10 p.m.
If you do need to get around, try taking C-470 and I-225.
(KUSA-TV © 2012 Multimedia Holdings Corporation with The Associated Press)