In patients with immune thrombocytopenia (ITP) refractory to corticosteroids and intravenous immunoglobulins (IVIG), splenectomy may result at higher risk of peri‐operative complications and, for this reason, potentially contraindicated. The thrombopoietin receptor agonists (TPO‐RAs) romiplostim and eltrombopag have shown high therapeutic activity in primary ITP, but data of efficacy and safety regarding their use in preparation for splenectomy are missing. Thirty‐one adult patients, median age 50 years, with corticosteroids and/or IVIG refractory persistent and chronic ITP who were treated with TPO‐RAs (romiplostim= 24; eltrombopag= 7) with the aim to increase platelet count and allow a safer execution of splenectomy were retrospectively evaluated. Twenty‐four patients (77%) responded to the use of TPO‐RAs with a median platelet count that increased from 11 × 109/L before starting TPO‐RAs to 114 × 109/L pre‐splenectomy, but a concomitant treatment with corticosteroids and/or IVIG was required in 19 patients. Twenty‐nine patients underwent splenectomy while two patients who responded to TPO‐RAs subsequently refused surgery. Post‐splenectomy complications were characterized by two Grade 3 thrombotic events (1 portal vein thrombosis in the patient with previous history of HCV hepatitis and 1 pulmonary embolism), with a platelet count at the time of thrombosis of 260 and 167 × 109/L, respectively and one Grade 3 infectious event. TPO‐RAs may represent a therapeutic option to improve platelet count and reduce the risk of peri‐operative complications in ITP candidates to splenectomy. An increased risk of post‐splenectomy thromboembolic events cannot be ruled out and thromboprophylaxis with low‐molecular weight heparin is generally recommended. Am. J. Hematol. 91:E293–E295, 2016. © 2016 Wiley Periodicals, Inc.