BACKGROUNDMedical emergency teams have been shown to reduce mortality in children's hospitals, but there are many potential barriers to their activation. Surveillance tools using electronic health record data help identify children at risk of deterioration. Existing early warning scores primarily include vital signs, but may benefit from the incorporation of medications.OBJECTIVEWe aimed to identify the therapeutic classes of medications temporally associated with clinical deterioration that could be incorporated with vital signs into surveillance tools.DESIGNCase‐crossover study.SETTINGThe Children's Hospital of Philadelphia.PATIENTSChildren with clinical deterioration, defined as cardiopulmonary arrest, acute respiratory compromise, or urgent intensive care unit transfer while hospitalized on pediatric wards (n = 141).EXPOSURESIntravenous administrations of medications from therapeutic classes administered in ≥5% of control periods.RESULTSNine therapeutic classes were significantly associated with clinical deterioration: glycopeptide antibiotics, anaerobic antibiotics, third‐generation and fourth‐generation cephalosporins, aminoglycoside antibiotics, systemic corticosteroids, benzodiazepines, loop diuretics, narcotic analgesics (full opioid agonists), and antidotes to hypersensitivity reactions.CONCLUSIONSWe identified a set of therapeutic classes associated with increased risk of clinical deterioration. Future work should focus on evaluating whether including these therapeutic classes in multivariable models improves their accuracy in detecting early, evolving deterioration. Journal of Hospital Medicine 2013;8:254–260. © 2013 Society of Hospital Medicine