Health-related quality of life (HRQoL) is a major concern for adults with chronic immune thrombocytopenic purpura (ITP) due to the symptoms associated with the disease and its treatment. This study utilized the ITP-patient assessment questionnaire (ITP-PAQ), a specialized HRQoL questionnaire for ITP, to investigate the humanistic burden of ITP and the impact of romiplostim therapy on HRQoL in two, placebo-controlled, phase 3 clinical trials of splenectomized and non-splenectomized patients. ITP-PAQ was self-administered to ITP patients at baseline, and weeks 4, 12 and 24 of treatment. Splenectomized patients had lower baseline HRQoL scores than non-splenectomized patients in seven of 10 scales (P < 0·05). After 24 weeks of romiplostim therapy, splenectomized patients showed significant improvements over placebo in four of 10 ITP-PAQ Scales (Symptoms, P = 0·0337; Bother, P = 0·0126; Social Activity, P = 0·0145; and Women’s Reproductive Health, P = 0·0184). Non-splenectomized patients demonstrated significant improvement over placebo in the Activity Scale (P = 0·0458). Data pooled from the two trials, adjusted for splenectomy status, showed significant improvement for romiplostim-treated patients in six scales; Symptoms, Bother, Activity, Fear, Social Activity and Women’s Reproductive Health. These results suggest that adult patients with chronic ITP have improved HRQoL following romiplostim therapy.