Deferiprone (DFP), deferasirox (DFX) and deferoxamine (DFO) are used in thalassaemia major (TM) patients to treat chronic iron overload. We evaluated the cost-effectiveness of DFP, compared with DFX and DFO monotherapy, from an Italian healthcare system perspective. A Markov model was used over a time horizon of 5years. Italian-specific cost data were combined with Italian efficacy data. Costs and quality-adjusted life years (QALYs) were calculated for each treatment, with cost-effectiveness expressed as cost per QALY. In all scenarios modelled, DFP was the dominant treatment strategy. Sensitivity analyses showed that DFP dominated the other treatments with a >99% likelihood of being cost-effective against DFX and DFO at a willingness to pay threshold of €20,000 per QALY. DFP was the dominant and most cost-effective treatment for managing chronic iron overload in TM patients. Its use can result in substantial cost savings for the Italian healthcare system.