According to Eysenck's theory of Introversion-Extroversion (I-E), introverts demonstrate higher levels of basal activity within the reticular-thalamic-cortical loop, yielding higher tonic cortical arousal than Extraverts, who are described conversely as chronically under-aroused and easily bored. We hypothesized that higher scores on the trait of Extraversion would be associated with greater declines in psychomotor vigilance performance during prolonged wakefulness. We evaluated the relationship between I-E and overnight psychomotor vigilance performance during 77 h of continuous sleep deprivation in a sample of 23 healthy adult military personnel (19 men; four women), ranging in age from 20 to 35 years. At baseline, volunteers completed the Revised NEO Personality Inventory (NEO PI-R) and completed psychomotor vigilance testing at approximately 10-min intervals from 00:15 to 08:50 hours over three nights of continuous sleep deprivation. In addition, 12 participants received four repeated administrations of caffeine (200 mg) every 2 h each night. Analysis of covariance and stepwise multiple regression analyses showed that, above and beyond the effects of caffeine, higher Extraversion was significantly related to more extensive declines in speed of responding and more frequent attentional lapses, but only for the first overnight testing session. Sub-factors of Extraversion, including Gregariousness and higher Activity level were most predictive of these changes following sleep loss. These findings are consistent with Eysenck's cortico-reticular activation theory of I-E and suggest that individual differences in the trait of Extraversion confer some vulnerability/resistance to the adverse effects of sleep loss on attention and vigilance.