This study is the fourth in a series examining driver fatigue in the Australian long distance road transport industry. Thirty-seven long haul truck drivers were measured on a routine 4500 km round trip. Two types of driving operations were compared, single driving, involving a solo driver, and two-up driving, where a pair of drivers operate a truck continuously and alternate between work and rest. Two-up drivers reported higher levels of fatigue than single drivers overall and tended to show poorer levels of performance. However, this result appeared to reflect differential fatigue at the start of the trip. Both two-up and single drivers showed marked increases in fatigue across the first half of the trip, followed by a substantial recovery of alertness and performance provided that drivers had stationary overnight rest at mid trip or had shorter trips. Fatigue continued to increase on the second half of the trip for drivers who did longer trips without the benefit of a substantial night rest or who did not have access to on-board rest, that is single drivers. The use of overnight rest, in combination with two-up driving, appeared to be the most successful strategy for managing fatigue across the trip.