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Sleepiness may account for up to 20% of crashes on monotonous roads, especially highways. Obstructive sleep apnea (OSA) is the most common medical disorder that causes excessive daytime sleepiness, increasing the risk for drowsy driving two to three times. The purpose of these guidelines is to update the 1994 American Thoracic Society Statement that described the relationships among sleepiness, sleep apnea, and driving risk.A multidisciplinary panel was convened to develop evidence-based clinical practice guidelines for the management of sleepy driving due to OSA. Pragmatic systematic reviews were performed, and the Grading of Recommendations, Assessment, Development, and Evaluation approach was used to formulate and grade the recommendations. Critical outcomes included crash-related mortality and real crashes, whereas important outcomes included near-miss crashes and driving performance.A strong recommendation was made for treatment of confirmed OSA with continuous positive airway pressure to reduce driving risk, rather than no treatment, which was supported by moderate-quality evidence. Weak recommendations were made for expeditious diagnostic evaluation and initiation of treatment and against the use of stimulant medications or empiric continuous positive airway pressure to reduce driving risk. The weak recommendations were supported by very low-quality evidence. Additional suggestions included routinely determining the driving risk, inquiring about additional causes of sleepiness, educating patients about the risks of excessive sleepiness, and encouraging clinicians to become familiar with relevant laws.The recommendations presented in this guideline are based on the current evidence, and will require an update as new evidence and/or technologies becomes available.