The authors used 2 national Veterans Health Administration databases to identify outpatient medications and all 30 Elixhauser comorbidities for 2579 unique patients, age 65+ years, hospitalized for syncope in fiscal year 2004. For comparison, we identified other elderly patients hospitalized with acute myocardial infarction (N = 4491), fracture (N = 2797), or pneumonia (N = 9473). The categories of medications included drugs that affect the cardiovascular, central nervous, or the muscular skeletal system. The most notable differences between syncope compared to acute myocardial infarction patients occurred in central nervous system drugs in anticonvulsants/barbiturates, antidepressants, antihistamine/antinauseants, antipsychotics, and cholinesterase inhibitors (P < .0018). Comparing syncope patients with fracture patients, the central nervous medication profile was similar, but the cardiovascular medication profile differed (P < .0018); their hypertension comorbidities also differed (60.45% vs 46.34%); (P < .0016). These findings indicate significant potential associations that warrant further study. Studies linking national outpatient medications to hospitalizations for specific conditions can foster the development of more proactive pharmacovigilance systems.