Not on my truck, happily enough, but my dad's '99 250 is damn near impossible to start. The ignition is very finicky about which keys it will allow to turn, and in some cases will only work with the key in a certain orientation, rather than either orientation being fine.

Will replacing the ignition lock cylinder fix this?

(I've assumed it will, but wanted to make sure before ordering any parts.)

 

Simplest and least expensive: Try a shot of lock lubricant. The tumblers may be sticking. I would try that first. Be careful with the product choice, stuff like WD-40 may gum up in cold weather.

Next, if you have a key that has had very little use, try it. If it works consistently get a copy made. Keys wear out too. If you don't have a little-used key, a dealership should be able to cut a new one with the VIN.

Then replace the cylinder. A good locksmith should be able to "key" it to your door locks. A '99 most likely pre-dates the keys with a chip, so no problem there.

I had a similar problem on my '82, and had to replace the cylinder. That cured it, BTW.

 

When I picked up the '99 SD that is now my son's truck, it came with one key and one keyfob.

Still working on the keyfob issue (programming), but, the ignition key was different than the door keys.

I looked online, and found a matched set of door locks and ignition lockset with 2 keys for less than $55.00 + shipping ($4.50).

Swapping the ignition lock cylinder is EASY, if you have one key that works the cylinder. (Less than 5 minute job.)

 

could be other factors ....had two fords that you had to play jiggle bug with sometimes to get the key to turn. sometimes it was so bad that it would only turn in neutral (with brakes on). turned out not to be the key cylinder or the keys.....turned out to be two screws behind the dask that held a bracket which supported some linkages to the tranny....the screws were loose and the bracket could be giggled. tighening the screws stiffend up the bracket and eliminated the key wont trun problem for a few months. then the problem came back as the screws got loose again. did the re-tightening and problem solved. happended a thrid time and this time I took the screws out and soaked them in green locktight. let the lcoktight dry, then put the screws back in. never came loose again and the key wont turn problem was solved for good.

so sure, it could be the key cylinder, could be the keys, and yes, can be other things.

Had another ford that had this problem and it turned out to be a switch on the brake pedal. the switch needed to be closed looped in normal operation...but one wire was frayed so sometimes it would be closed loop and somethimes it would not. So sometimes the key turned and sometimes it would not. After cutting the wires and re-terminating it, reinstalled it and that key wont turn problem when away.

had another ford that the key would not turn. that car was underwater for 6 hours. no fix for that one...sent it to the junk yard

proceed with open mind.

 

Its a 5 minute job as long as the lock will still turn!

The key in my 03 E150 with 50k on it had never given me a single problem, drove over to my moms house shut it off and when I went to leave the key refused to turn. There it sat at 7:00 at night with the power windows rolled down and parked on the street. I tried everything but that key never turned again. I had to drop the column and get to the actual ignition switch, I was able to turn it on and roll the windows up but the wheel was locked so I still couldn't drive it.

I ended up pulling the column and drilling the lock cylinder out. I pulled the column because I didn't want all the filings going down inside the column. I talked to a friend who is a tech at the local dealer, he said the shop has had to drill a few out and quoted about $350 for the job. Take my advice if you are having trouble with it don't put it off, get the cylinder replaced. I bought a motorcraft lock cylinder and it came with the extra tumblers to re-key it to my key.