Study Objectives: Obstructive sleep apnea (OSA) is associated with driving impairment and road crashes. However, daytime function varies widely between patients presenting a clinical challenge when assessing crash risk. This study aimed to determine the proportion of patients showing "normal" versus "abnormal" driving simulator performance and examine whether anthropometric, clinical, and neurobehavioral measures predict abnormal driving. Methods: Thirty-eight OSA patients performed a 90-min simulated driving task under 3 conditions: normal sleep, restricted sleep (4 h in bed), and normal sleep + alcohol (BAC∼0.05 g/dL). Patients were classifi ed as "resilient" drivers if, under all 3 experimental conditions their mean steering deviation fell within 2 standard deviations of the mean steering deviation of 20 controls driving under baseline normal sleep conditions, or a "vulnerable" driver if mean steering deviation was outside this range in at least one experimental condition. Potentially predictive baseline anthropometric, clinical, neurocognitive, and cortical activation measures were examined. Results: Of the 38 OSA patients examined, 23 (61%) and 15 (39%) were classifi ed as resilient and vulnerable drivers, respectively. There were no differences in baseline measures between the groups, although the proportion of females was greater and self-reported weekly driving exposure was less among vulnerable drivers (p < 0.05). On univariate analysis gender, weekly driving hours, and auditory event related potential P2 amplitude were weakly associated with group status. Multivariate analysis showed weekly driving hours (OR 0.69, 95%CI, 0.51-0.94, p = 0.02) and P2 amplitude (OR 1.34, 95%CI 1.02-1.76, p = 0.035) independently predicted vulnerable drivers. Conclusions: Most OSA patients demonstrated normal simulated driving performance despite exposure to further sleep loss or alcohol. Most baseline measures did not differentiate between resilient and vulnerable drivers, although prior driving experience and cortical function were predictive. Novel measures to assist identifi cation of OSA patients at risk of driving impairment and possibly accidents are needed. Trial Registration: Data presented in this manuscript was collected as part of a clinical trial "Experimental Investigations of Driving Impairment in Obstructive Sleep Apnea." Trial ID: ACTRN12610000009011, URL: http://www.anzctr.org.au/trial-view.aspx?ID=334979.