OBJECTIVES: This analysis examined potential risk factors for adverse drug reaction (ADR)-related hospitalizations and compared seniors’ drug therapy pre-admission and post-discharge to see whether hospitalization led to changes in drug therapy. METHODS: This analysis used hospital discharge data from the Discharge Abstract Database and drug claims data from the National Prescription Drug Utilization Information System Database to assess potential risk factors for ADR hospitalizations among seniors on public drug programs in Alberta, Manitoba and P.E.I. RESULTS: The number of drugs was the most significant risk factor, with seniors taking 15 or more drugs 6.4 times more likely than seniors taking fewer than 5 drugs to have been hospitalized for an ADR. Other factors associated with hospitalizations for ADRs were patient age and being hospitalized in the previous year. The relationship between new drug starts and ADR-related hospitalizations varied by drug class. 33.2% of seniors hospitalized for an opioid-related ADR started taking an opioid within 30 days of hospitalization, while only 28.2% of seniors hospitalized for an anticoagulant-related ADR started an anticoagulant within a year of hospitalization. CONCLUSIONS: Although it is often necessary for seniors to take multiple drugs to manage their chronic conditions, regular medication reviews can help reduce the risk of adverse events including drug interactions. A high proportion of the hospitalizations related to anticoagulant ADRs occurred more than a year after starting therapy, which underscores the importance of ongoing monitoring.