Home-hospitalization (HH) improves clinical outcomes in selected patients with chronic obstructive pulmonary disease (COPD) admitted at the emergency room due to an exacerbation, but its effects on healthcare costs are poorly known. The current analysis examines the impact of HH on direct healthcare costs, compared to conventional hospitalizations (CH). A randomized controlled trial was performed in two tertiary hospitals in Barcelona (Spain). A total of 180 exacerbated COPD patients (HH 103 and CH 77) admitted at the emergency room were studied. In the HH group, a specialized respiratory nurse delivered integrated care at home. The average direct cost per patient was significantly lower for HH than for CH, with a difference of euro 810 (95% CI, euro 418-1,169) in the mean cost per patient. The magnitude of monetary savings attributed to HH increased with the severity of the patients considered eligible for the intervention.