The long-term impact of COVID-19 disease is becoming a major global concern. In this retrospective monocentric analysis, we included consecutive subjects admitted to our COVID-19 Post-Acute Care Service for a SARS-CoV-2 infection that occurred between three and twelve months before. A home medication list relative to the period before SARS-CoV-2 infection (baseline) was recorded and compared with that one relative to the time of outpatient visit (follow-up). Drugs were coded according to the Anatomical Therapeutic Chemical Classification (ATC) System. In a total of 2007 subjects, at follow-up, a significant increase with respect to baseline was reported in the total median number of chronic medications (two [0-4] vs. one [0-3]) and in specific ATC-group drugs involving the alimentary, blood, cardiovascular, genitourinary, muscle-skeletal, nervous and respiratory systems. In a multivariate analysis, COVID-19 disease severity and age > 65 years resulted in the best predictors for an increase in the number of medications, while anti-SARS-CoV-2 vaccination played a significant protective role. The long-term care of patients infected by COVID-19 may be more complex than reported so far. Multidisciplinary and integrated care pathways should be encouraged, mainly in older and frailer subjects and for patients experiencing a more severe disease. Vaccination may also represent a fundamental protection against long-term sequelae.