To compare the incidence of hospitalization for upper gastrointestinal bleeding in patients using individual anticoagulants with and without PPI cotherapy and to determine variation according to underlying gastrointestinal bleeding risk, a retrospective cohort study in Medicare beneficiaries was carried out between January 1, 2011 and September 30, 2015. The agents studied included apixaban, dabigatran, rivaroxaban, or warfarin, with or without PPI cotherapy.