Older adults are at increased risk of hospitalization due to COVID-19 infections. This study examined the potential severe drug-drug interactions (DDI) among hospitalized older adults taking two or more medications at admission and discharge. There was a significant increase in prescription of proton pump inhibitors and heparins from admission to discharge. Clinical decision support systems should be used to assess potential DDI with particular attention paid to the risk of bleeding complications linked to heparin-based DDIs.