Aim. To analyse the diagnosis-related characteristics and the costs of treating patients with difficult/prolonged weaning from mechanical ventilation we have undertaken a retrospective observational study. Methods. The study has considered all the patients admitted to our weaning unit of a regional Rehabilitation department during 3 consecutive periods since the opening date. Characteristics of the admitted patients and the DRG-related cares delivered have been recorded. A cost analysis has been obtained over time. Results. The number of beds allocated to this unit (from 4 in the 1st period to 6 in the 2nd and 3rd periods) and the number of patients cared for (from 32 to 43 and to 65, respectively) increased over time. In particular, the COPD to non-COPD patient ratio (from 2.2 to 1.3 and to 1.0) and the DRG/patient weight (from 3.0±0.3 to 3.1±0.2 and to 3.3±0.2 point) changed significantly (p<0.05). The daily reimbursement per patient from the public health care system only slightly increased, whereas the operating margin (reimbursement less costs) per patient significantly improved (from -304, to +17 and +55 €/pt/day, respectively, p<0.05) due to a gradual restriction in the variable costs. Length of stay, mortality rate and weaning rate did not change over time. Conclusion. The weaning centre is a hospital area where economic burdens should be carefully evaluated. Given the actual reimbursement received on a national level for these patients, variable costs might be better spread, thus optimising the burdens without losing out on clinical outcomes.