Background: Concerns regarding the effects of fatigue on physician performance and quality of life lead to the implementation of duty hour restrictions for residents by the Accreditation Council for Graduate Medical Education (ACGME). These restrictions have been met by strong criticism from the neurosurgical community. This is partly due to a lack of objective evidence that fatigue results in decrements in professional function in neurological surgeons. There is also concern that the restrictions have diminished clinical and operative experience as well as the development of professional responsibility in residency.Objective: To evaluate whether 24-hour neurosurgical call has an objective impact on fine motor dexterity, cognitive thinking skills, and mental well-being.Methods: Subjects were tested before and after taking 24 hours of neurosurgical call. We evaluated fine motor dexterity using the Vienna Test System Motor Performance Series, cognitive thinking abilities using a battery of paper-pencil neuropsychological tests, and mental well-being using the Profile of Mood States. Results: A total of 27 subjects were included in this study, 12 seasoned to neurosurgical call and 15 naive to neurosurgical call. The seasoned subjects demonstrated no statistically significant change in performance after call on any of the tests for fine motor dexterity or cognitive thinking abilities. The nonseasoned subjects demonstrated multiple decrements in fine motor dexterity and cognitive thinking abilities after taking call. In the Motor Performance Series, they had a statistically significant decrease in the speed of untargeted movements in the nondominant hand during the tapping test (p = 0.002), and a decline in the precision of fine motor movements and information processing as evidenced by an increase in the number of errors of the dominant hand in the line tracking test (p = 0.014). There was a statistically significant decline in their immediate memory during Hopkins Verbal Learning Test (p = 0.025), and complex attention, mental flexibility, and visual-motor speed in the Trail Making Test (p = 0.03). The Profile of Mood States found no difference in feelings of anger (p = 0.54), tension (p = 0.358), or depression (p = 0.65). There were increased feelings of confusion (p < 0.001) and decreased feelings of vigor (p < 0.001) and friendliness (p = 0.001). Nonseasoned subjects had an increase in total mood disturbance (p = 0.012) but seasoned subjects did not (p = 0.083). Conclusion: Our results suggest that fatigue-induced decrements in professional function can be ameliorated by experience with prolonged duty hours. In contrast to nonseasoned subjects, those who were conditioned to 24-hour neurosurgical call demonstrated resilience in fine motor dexterity and cognitive thinking skills, and exhibited no change in total mood disturbance. An argument can be made that we are turning the neurosurgical training paradigm upside down with the current ACGME duty hour restrictions.