Objective: Adult chronic immune thrombocytopenic purpura (ITP) is characterized by autoimmune-mediated platelet destruction and suboptimal platelet production. Signs and symptoms can range from bruising to gastrointestinal and intracranial bleeding. The disease may therefore impact one's health-related quality of life (HRQoL). We quantified the burden of ITP on patient-reported HRQoL. Methods: We compared baseline Short Form (SF)-36 scores for individuals with ITP who enrolled in one of two double-blind, randomized clinical trials for the treatment of ITP [one group was refractory to splenectomy (n = 58) and the other had no splenectomy (n = 60)] to general populations in Canada (n = 9,408) and the US (n = 2,474). We also compared ITP-specific HRQoL burden using the ITP-Patient Assessment Questionnaire (PAQ) across platelet count categories (<10 x 109/L vs. 10 to 49 x 109/L). ANOVA tests were used to compare age and sex-adjusted means across samples. Results: The mean age of the ITP patients was 53.3 ± 16.2 years, and the majority (64%) was female. SF-36 scores of ITP patients were significantly (p<0.0001) worse than those from the Canadian and US general population for each scale and summary score. The largest differences were found for physical functioning (67.2 vs. 85.8 and 80.8); role functioning-physical (42.3 vs. 82.1 and 77.0); general health (49.4 vs. 77.0 and 69.9); vitality (40.4 vs. 65.8 and 60.0), and role functioning-emotional (60.5 vs. 84.0 and 80.1). In addition to statistical significance, these differences were clinically meaningful. ITP patients with lower platelet counts also had worse SF-36 and ITP-PAQ scores, particularly for symptoms (50.8 vs. 67.8; p<0.001); fear (65.0 vs. 78.9; p<0.05), and social activity scales (59.6 vs. 75.5; p<0.05) of the ITP-PAQ. Conclusion: ITP was found to impact both physical and psychological aspects of HRQoL.