Have a 2000 F-250 V-10 4x4 with 335,000 miles on the clock. Has started hesitating at 40-45. You can't really notice it at idle. Drove it around at lower speeds and just a miss here and there. Take it up to 40-45 and it's quite bad. Hasn't thrown any codes. Hooked it up to the scanner to get no additional info. My gut says coil packs but am kinda confused that I haven't gotten a misfire code yet. Any other ideas to check?

 

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Most likely is spark plugs. While you are in there changing them inspect the coil boots. With that many miles, if you don't remember when the boots were changed last it is probably best to plan on changing all of the boots.

 

So what makes the spark plugs do this? I will be replacing the coil packs while I am at it.

 

Not sure that it is the spark plugs for sure, but excessive wear from leaving them in for too many miles can cause them to fall apart.
The rubber coil boots can get misshapen over time. This can cause the end that fits over the spark plug to relax and widen out enough that it can leak from either dirt or moisture and can cause the coil's discharge energy to short circuit to the edge of the plug well instead of through the center of the plug like it is supposed to. Or the rubber can develop cracks that can also make it leak.
Whatever the cause of a misfire, the spark plug on the misfiring cylinder should be changed for a new one.

 

Pull the vacuum line off the EGR valve and see if it improves. If it does it may not be an EGR problem, could be elsewhere and the EGR cutting in just amplifies the problem.

 

Where is the EGR located on these trucks? I hate to sound stupid but I am normally used to knowing my way around my 7.3, not the V-10.

 

I had something similar on my '99' 5.4 which had fresh plugs, cleaned the MAF sensor, filters and after taking the throttle body off and cleaning it which was pretty nasty in side the problem went away. Just throwing it out there.