Background Military aviation in distant operations increases aircrew fatigue and the risk of human-factor-related safety incidents. This study evaluated the impact of different fatigue management and pharmacological human augmentation approaches on flight safety and, in a separate analysis, the effect of prior spatial disorientation (SD) simulator training on in-flight SD severity.Methods We retrospectively reviewed human-factor-related safety incidents in the Israeli Air Force across three operational periods: Operation 'Iron Swords' (short-range, lower-tempo), 'Rising Lion' (12-day long-range, high-tempo) and 'Epic Fury' (42-day extended-duration, high-tempo). The primary outcome was the normalised rate of safety incidents per flight hour. Secondary outcomes included the normalised utilisation of caffeine and modafinil and the severity of SD events among trained versus untrained aircrew.Results Across the three periods, 949 incidents were reported. Normalised incident rates and severity distributions remained stable between 'Rising Lion' and 'Epic Fury', despite the latter's significantly greater flight volume. The fighter fleet, the only platform to fully implement preplanned, individualised flight-and-rest scheduling and personalised stimulant prescriptions, was also the only platform to demonstrate a decrease in normalised incident rates (r=-0.82, p=0.004). Aircrew who had never undergone SD simulator training sustained significantly more severe SD events than previously trained aircrew (p=0.015).Conclusions Implementing individualised physiological envelopes-combining personalised pharmacological augmentation with structured rest-was associated with stable or reduced in-flight safety incident rates during sustained, high-tempo operations. Additionally, prior SD simulator training was associated with a decreased level of severity of SD events.
