The purpose of this study is to assess prescription medication poisoning among psychoactive and nonpsychoactive medications used by elderly (65 years or older) Medicare & Medicaid dual enrollees as well as examine contextual components associated with poisoning. Our primary research goal was to compare medication poisonings among psychoactive medications to nonpsychoactive medications. Our second research goal was to identify components influencing medication poisonings and how they interrelate. The approach used a cross-sectional retrospective review of calendar year 2003 Centers for Medicare & Medicaid Service's Medicaid Pharmacy claims data for elderly dual enrollees. Poisonings were identified based on ICD-9-CM categorizations. Poisonings associated with the psychoactive medications were proportionally over twice as high as compared to nonpsychoactive medications (14.3 per 100,000 enrollees and 6.6 per 100,000 enrollees, respectively). Additionally, the two contextual components of (a) use of many drugs and (b) familiarity with the medication have a direct, but competing impact on poisoning. The reasons behind unintentional poisoning in the elderly have been somewhat a mystery. This study is among the first to attempt to distinguish between poisoning events associated with psychoactive medications versus nonpsychoactive medications as well as assess the impact of differing contextual components on medication poisoning.