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N=60 commercial airline pilots holding valid ATPLs flew a manual ILS approach following a weather induced missed approach during a night mission in full flight simulators. Measures of subjective fatigue, sustained attention, and the NASA Taskload Index were collected before and after the mission. In addition, sleep history data were available covering three days prior to the simulator. Both subjective and objective measures of fatigue showed significant ascent over the three hours of the experimental procedure. While sleep history data and roster information were related to both the overall level of fatigue and to reaction times, pilots who experienced a higher degree of workload during the simulator exercise showed a significant increase in subjective fatigue scores after the mission. The findings provide some evidence for lasting effects of a sleep deficit as well as for a multifactorial model of fatigue risk.