This study aims to describe the epidemiological and clinical characteristics and trends of these admissions in Spain. This retrospective study drew data from the Hospital Discharge Records Database of the Spanish National Health System. We used the diagnostic codes for leprosy from the International Classification of Diseases, ninth and tenth revisions, to retrieve leprosy admissions from 1997 to 2021. There were 1387 hospitalizations for leprosy The number of annual cases decreased gradually, from 341 cases in 1997–2001 to 232 in 2017–2021 (p < 0.001). Patients’ median age increased, from 65 years in 1997–2001 to 76 years in 2017–2021 (p < 0.001), as did the prevalence of some comorbidities, such as hypertension (15% in 1997–2001 to 27.6% in 2017–2021; p < 0.001). The mortality rate (6%) and the frequency of leprosy complications remained stable. After Spain (79.1%), the most common country of origin was Paraguay (4.4%). Admissions decreased significantly in Andalusia, from 42% in 1997–2001 to 10.8% in 2017–2021 (p < 0.001), and in the Canary Islands, from 7.9% in 1997–2001 to 2.6% in 2017–2021 (p = 0.001), whereas they increased in Madrid, from 5.9% in 1997–2001 to 12.1% in 2017–2021 (p = 0.005). Overall, leprosy admissions in Spain have declined, even in the regions with the highest prevalence. Patients admitted for leprosy have become older and sicker.