Do you mean physically just unhooking the unit/cable from the OBDII port? Yes, nGauge does not require it to be attached to the truck and will not affect anything if removed. Mine is in my glove box and has never stayed hooked up. I use an Edge CTS2 for a monitor and only use the nGauge to program the truck, then remove it. If by unhooking you mean returning to stock programming wise, then unhooking it while youre ******d, then yes, you will have issues.