We here describe a single-institution experience on 40 patients with myelodysplastic syndromes (MDS) consecutively treated with deferasirox at the dose of 10-30 mg/kg/day according to Consensus Guidelines on Iron Chelation Therapy, outside of clinical trials. Serum ferritin (SF) was measured monthly, and safety assessment included monitoring of adverse events during treatment and of liver and renal parameters. Median SF at baseline of the 40 patients was 2,878 ng/ml. Median dose of deferasirox was 1,125 mg/day. At a median follow-up of 12 months of treatment, there was a significant reduction in SF from baseline, the median value being 1,400 ng/ml (p = 0.001). Interruptions due to toxicity were recorded in 40 % of patients: most common adverse events were diarrhoea (five patients, 12.5 %) and skin rash (four patients, 10 %). Seven patients had increased serum creatinine values >33 % above baseline, but there were no progressive increases. Four patients (three refractory anaemia and one refractory anaemia with excess blasts type 1) had a reduction of transfusion requirement (from a median of 5 to 1 unit/month) according to International Working Group 2006 criteria, with mean Hb value increasing from 8.5 to 10.5 g/dl, and mean Hb improvement being 2 g/dl (p = 0.02). No increased toxicity was noted when deferasirox was used concomitantly with azacitidine (eight patients who were intermediate 2 International Prognostic Scoring System risk) or lenalidomide (two patients with del(5q)). In conclusion, the oral iron chelator deferasirox is effective and safe when used in MDS patients with transfusion requirement, also if administered concomitantly with other drugs.