2006 E350 5.4l 95k.

Driving down freeway and check engine light came on. I could tell it was an immediate misfire/lack of firing in one cylinder. Check engine light would blink on and off. I was 8 miles from home so I was going to turn around. As I slowed down on the off ramp check engine light went off and engine ran fine. So I turned around and headed home. When I got to top speed again, same thing happened. After about 1-2 minutes it went back off again. This happened about 2-3 more times until I made my exit where it went off and stayed off all the way home about 2-3 miles on surface streets. I pulled the codes a I got P0300 Random misfire on cylinders 3,4,5,and 7. I replaced plugs about 5,000 - 10,000 miles ago with factory Motorcraft. No issues until this point. Any ideas where to start?

 

Double check the COP boots, making sure they're still (mostly) water tight and making good contact.

Also check the COP connections from the wiring harness--they've been known to work loose if the locking tabs have broken.

Also follow the COP larger wiring harness where they lead into larger bundles-----they should be paired with the injector wiring, a pair of them, one for each side of the engine.

Look for corroded contacts inside the larger connector shells.

Its not likely your ECM or crank trigger are at fault----those would throw more definite DTC's.

 

Possibly a plugged cat in the making. Drive it and clear the codes a couple times to make sure it's not a particular COP as mentioned by JWA. If you don't see a consistent COP at fault and don't notice performance problems, I would ignore it until you have a significant performance issue. If at some point you notice low power / sluggish power, pull the down stream O2 sensor from bank 2 (the one with the more crooked pipe) and see if you regain power. It'll be a loud ride, but this is a good test for a bad cat. If you do get your power back, the cat is plugged. Replace with 49 state legal Eastern Catalytic aftermarket part unless you reside in California.

You usually see more 5-8 cylinder misfires when the #2 bank is plugged. (p0305-p0308). The #2 cat bank plugs up more often because the cat pipe is crooked on that bank. You might still see 1-4 misfires since the #1 cat bank might be not that great either and the bad situation on 5-8 can throw off 1-4 also.

Only other thing that comes to mind is the EGR valve. Your 5.4 probably doesn't have one so that's most likely a non issue but I'm not sure if some 5.4L's did have an EGR. I've had those go bad every now and then on our 4.6L and cause flashing check engine lights.

 

I had a P0300 code with a P0303, and P0306 on my wifes car a week or so ago. One of the coil packs was bad, replaced all of them. A week later #1 stopped firing so I replaced all plugs and wires.

Just saying, because it's certainly not a Ford V8.