Glucocorticoid treatment is the standard initial therapy for patients with immune thrombocytopenia (ITP). Despite a rate of 60-80% of initial remissions, only 30 to 50% of adults have a sustained response after discontinuation. Second line options are splenectomy, thrombopoietin-receptor agonists (TPO-RAs), rituximab and intravenous immunoglobulin. Third line treatments include a mix of immunosuppressive drugs (e.g. azathioprine, ciclosporin, etc.). Recently international guidelines have proposed a treatment algorithm formalizing TPO-RAs and splenectomy as second and third line respectively, confirming splenectomy as second line choice only in emergency. Here we present a single center observational retrospective study of eltrombopag as second line treatment. We evaluated 48 adult primary chronic ITP patients since 2003. Forty-four out of 48 patients received a first line treatment with glucocorticoids. Twenty-two (61%) patients needed a second line treatment: 18 received eltrombopag, 3 a second course of steroid and one patient underwent splenectomy. Every patient before starting eltrombopag or receiving splenectomy underwent bone marrow examination. Overall response rate to eltrombopag was 94% with a CR rate of 76% and a PR of 23%; only one patient was non responder, underwent splenectomy and received subsequent treatment with rituximab, romiplostim and cyclosporin obtaining CR. One patient developed an autoimmune pancytopenia about a month after starting TPO-RA and in addition to eltrombopag received steroid and rituximab with blood count improvement. After a median follow up of 21,1 months (range 0,4-64,7 months) 16 patients (89%) are still on therapy maintaining response. As regards safety, gastrointestinal side effects were rare and low grade; only one patient discontinued eltrombopag after few weeks, because of dizziness. One patient had a relapse of deep venous thrombosis while no major bleeding complications were observed. Our real-life single center experience confirms efficacy and safety of eltrombopag as second line treatment in chronic ITP patients.