This is a cut and paste off a forum I often frequent.
Common weak links in the motor:
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Head bolts. A poor engineering design for connecting the heads to the block frequently results in head bolts that stretch and blown head gaskets. The telltale is coolant being forced out of the degas (coolant reservoir) bottle. Look for white residue on the bottle, underneath the bottle, and on the underside of the engine hood (where the hood rests above the bottle). You’ll also often hear a tea-kettle whistle when under boost (accelerating). The rub? To prevent blown head gaskets, you’ll need to upgrade to head studs. And check the heads for cracks. And check the heads for flatness. If the heads aren’t in specs, head studs are just wasted money. My truck has had new heads (once) and head studs (twice).
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Oil coolers. Silicate in the coolant falls out of suspension, is superheated, forms a snot like substance, and clogs the oil cooler. Telltale is a EOT / ECT difference greater than 15*. Also causes coolant puking out of the degas bottle. If they crack, coolant and oil co-mingle and they don’t play well together. The oil cooler isn’t terribly expensive, but the labor to replace it is. I replaced mine as preventative maintenance. A coolant filter will help capture the silicate that will fall out of suspension and help prolong the life of the oil cooler.
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FICM (Fuel Injection Control Module). Ford updated the PCM strategies many times over the years the 6.0 was in production, and some of these strategies weren’t tolerated well by the FICM. They’ll fail with little to no warning. A healthy FICM should put out 47-48v under all conditions (KOEO, cranking, running, and after the motor is up to full temp. Low voltage (under 45v) under any one of these conditions indicates a FICM that’s on it’s last leg. I’ve replaced mine twice.
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Injectors. Although the 6.0 injectors are less complex than the 7.3 injectors, they’re much more sensitive to poor fuel quality, low fuel pressure, or low voltage (see FICM). Some owners have great luck with them, and others have gone through 17 injectors in 20k miles or less. All “new” injectors from Ford are remans, but they come with a 12 month/12k mile warranty. I replaced 8 injectors at 135k miles (35k on veg oil).
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EGR cooler. These are known to crack and allow coolant into places it was never meant to be. A quality EGR delete kit is almost a must have on these trucks.
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Up pipes. Also referred to as a Y-pipe, it’s the pipe(s) that comes off of the exhaust manifold and bolt onto the back of the turbo. There are two flex sections that have a tendency to crack, and when they do you have an exhaust leak. Open the hood and have someone watch the back of the motor while you blip the throttle. If you see exhaust coming from behind the motor, either the pipe isn’t connected properly or something is cracked. You’ll also hear something that sounds close to the tea kettle whiste that accompanies blown head gaskets. My flex sections were cracked and I replaced the up pipe.