International commercial airline pilots may experience heightened fatigue due to irregular sleep schedules, long duty days, night flying, and multiple time zone changes. Importantly, current commercial airline flight and duty time regulations are based on work/rest factors and not sleep/wake factors. Consequently, the primary aim of the current study was to investigate pilots' amount of sleep, subjective fatigue, and sustained attention before and after international flights. A secondary aim was to determine whether prior sleep and/or duty history predicted pilots' subjective fatigue and sustained attention during the international flights. Nineteen pilots (ten captains, nine first officers; mean age: 47.42+/-7.52 years) participated. Pilots wore wrist activity monitors and completed sleep and duty diaries during a return pattern from Australia to Europe via Asia. The pattern included four flights: Australia-Asia, Asia-Europe, Europe-Asia, and Asia-Australia. Before and after each flight, pilots completed a 5 min PalmPilot-based psychomotor vigilance task (PVT) and self-rated their level of fatigue using the Samn-Perelli Fatigue Checklist. Separate repeated-measures ANOVAs were used to determine the impact of stage of flight and flight sector on the pilots' sleep in the prior 24 h, self-rated fatigue, and PVT mean response speed. Linear mixed model regression analyses were conducted to examine the impact of sleep in the prior 24 h, prior wake, duty length, and flight sector on pilots' self-rated fatigue and sustained attention before and after the international flights. A significant main effect of stage of flight was found for sleep in the prior 24 h, self-rated fatigue, and mean response speed (all p < 0.05). In addition, a significant main effect of flight sector on self-rated fatigue was found (p < .01). The interaction between flight sector and stage of flight was significant for sleep in the prior 24 h and self-rated fatigue (both p < .05). Linear mixed model analyses indicated that sleep in the prior 24 h was a significant predictor of self-rated fatigue and mean response speed after the international flight sectors. Flight sector was also a significant predictor of self-rated fatigue. These findings highlight the importance of sleep and fatigue countermeasures during international patterns. Furthermore, in order to minimize the risk of fatigue, the sleep obtained by pilots should be taken into account in the development of flight and duty time regulations.