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The FAA Office of Aerospace Medicine sets medical standards needed to protect the public and pilots from death or injury due to incapacitation of the pilot. As a part of this process, toxicology testing is performed by the FAA on almost every pilot who is fatally injured in an aviation accident to determine the medical condition of the pilot, medications used by the pilot at the time of the accident, and the extent of impairment, if any. The data were extracted from the FAA toxicology database for all pilots who died from 2004 and 2008 in aviation accidents. The laboratory received and tested specimens from 1,353 pilots who died in aviation accidents between 2004 and 2008. Findings were classified into three separate categories: Controlled Dangerous Substance, Prescription, and Over-the-Counter drugs. The study was conducted to determine the extent of drug use in pilots who have died in aviation accidents from 2004 to 2008 and to determine the types of drugs most commonly found. A comparison of previously published reports with this study's report was made to determine trends in drug use by pilots who have died in aviation accidents over the past 20 years. Factors were examined that could influence drug trends noted over the years. Diphenhydramine, an H1 antihistamine with impairing properties, is the most common drug found in pilots who have died in aviation accidents. The FAA has taken steps to warn pilots of the dangers of using this medication, which is dispensed as both a prescription and an over-the-counter medication. Because significant aviation performance impairment can be associated with diphenhydramine, the Office of Aerospace Medicine will continue to take steps to help pilots decide when it is safe to resume flying duties after taking such an impairing medication.