Bleeding is of particular clinical importance in the management of chronic immune thrombocytopenia (ITP), which involves impaired platelet production and accelerated destruction. We report the first comprehensive analysis of the impact of eltrombopag on bleeding in five clinical studies of adult chronic ITP: two 6-week phase 2 (TRA100773A) and phase 3 (TRA100773B) studies; a 6-month phase 3 study (RAISE); a phase 2 repeat-dose study (REPEAT); and a phase 3 extension study (EXTEND). Bleeding was assessed using the World Health Organization Bleeding Scale and categorized as no bleeding (grade 0), any bleeding (grades 1–4), and clinically significant bleeding (grades 2–4). Bleeding was also assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Across all studies, bleeding at baseline ranged from 50 to 73% for eltrombopag-treated patients; by week 2, bleeding had decreased, ranging from 26 to 39%. This trend was maintained throughout treatment. Similar results were observed for clinically significant bleeding. No such trend was seen in placebo-treated patients for any bleeding or clinically significant bleeding. For TRA100773B and RAISE, the odds of any bleeding across the entire treatment period were 51 and 76% lower for eltrombopag-treated versus placebo-treated patients (P = 0.021, P < 0.001). The odds of clinically significant bleeding in RAISE were 65% lower (P < 0.001). In conclusion, analysis of prospective data from five clinical studies demonstrates that eltrombopag significantly reduces bleeding in adult patients with chronic ITP.