INTRODUCTION: Fatigue is a common problem in aviation. The identification of efficacious fatigue countermeasures is crucial for sustaining flight performance during fatigue-inducing operations. Stimulants are not recommended for consistent use, but are often implemented during flight operations with a high risk of fatigue. As such, it is important to evaluate the efficacy of approved stimulants for sustaining flight performance, alertness, and mood.METHODS: Four electronic databases (PubMed, PsycInfo, SPORTDiscus, Web of Science) were systematically searched to identify research on the effects of caffeine, dextroamphetamine, and modafinil during simulated or in-flight operations.RESULTS: There were 12 studies identified that assessed the effects of at least 1 stimulant. Overall, dextroamphetamine and modafinil were effective for sustaining flight performance and pilot mood during extended wakefulness. Results with caffeine were inconsistent.DISCUSSION: Dextroamphetamine and modafinil appear to sustain flight performance and mood during extended wakefulness. However, most studies have used flight simulators and short operation durations. Additional research is needed in realistic settings and during longer duration operations. Caffeines effects were inconsistent across studies, possibly due to differences in study methodology or individual caffeine responses. Despite fatigue being a common problem in civilian aviation as well, only one study in this review included civil aviators. More research should be conducted on the effects of caffeine during civil operations.CONCLUSION: Dextroamphetamine and modafinil appear to be effective fatigue countermeasures but should be further evaluated in more ecologically valid settings. The effects of caffeine are unclear at this time and should continue to be evaluated.Ehlert AM, Wilson PB. Stimulant use as a fatigue countermeasure in aviation. Aerosp Med Hum Perform. 2021; 92(3):190200.