Yes. I have used my gurus with all sorts of configurations involving kettles (both 22.5 and 18.5). Two things are important - 1. where you drill your hole for the fan 'adaptor' and 2. that your lid is not bent and forms a tight seal with the grill when shut.
I have tried and do not like putting the fan/adaptor on the lid vent for a several reason. Drill your hole on the bottom high enough up that when the adaptor is attached you can still use the ash sweeper , but not too much higher so that you can still put the coal grate over top of it. You want to make sure it creates a clean draft that sweeps underneath the coals.
If I am using the kettle/guru combo for a long smoke, I use welding tape to seal the bottom air slits. I also use the same welding tape to seal the holes on the lid vents (with the vent cover in the open position). Then I poke my thermometers through one of the tape-covered holes, allowing for the smallest possible air leakage.
The biggest down side is when you take the lid off, you lose an enormous amount of the heat you just built up and the guru will immediately start compensating and over stoke the fire. Sometimes the immediate introduction of air after a long smoke may cause grease drippings on the sides of the kettle or in a drip pan from a brisket to suddenly combust.
If you have the DigiQ II it does an okay job of detecting when the lid is off (by the sudden drop in temp) but I wouldn't always rely on it. I would make sure you turn off your guru before you take off the lid.
Also, if you have one of the original gurus make sure when you turn it back on you don't turn it on in ramp mode (unless that is what you want). That has tripped-me up at 4 in the morning more than once.
