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Blood donor screening is performed to accomplish several goals, including donor safety during collection and recipient safety during transfusion. Donors taking certain medications such as teratogens or platelet-inhibiting drugs are deferred from donation. Studies investigating the accuracy of the donor history are limited and only provide data on select groups of drugs. This study compares the results of an extended serum toxicology analysis to the medication use reported on the donor questionnaire.Whole-blood samples were collected from 108 volunteer blood donors. A serum toxicology analysis was performed with high-performance liquid chromatography with photodiode array detection. The results were compared to those reported on the donor history questionnaire.The medication history was consistent with the reported medications in 96 (89%) donors. Serum toxicology testing detected medications that were not reported on the donor history form in 12 (11%) donors. Most of the donors who did not accurately report their medication use (8 or 67%) were taking psychotropic medications.Eleven percent of the donors did not fully disclose their recent medication history. Although none of the omitted medications would have been grounds for deferral, the finding of underreporting questions the reliability of donor screening. Despite a negative medication history, blood donor centers cannot assume that donors are medication-free. This study reveals a bias to omit psychotropic medications such as antidepressants and anxiolytics.