OBJECTIVES: To conduct a systematic review of the literature and assess the impact of orthopaedic surgery on the health-related quality of life (HRQoL) of haemophilia patients with or without inhibitors. METHODS: Searches were conducted in the MEDLINE, EMBASE, EconLit, Cochrane library and the Center for Reviews and Dissemination databases from 2000 onwards. A broad search including both Medical Subject Heading (MeSH) terms and key words related to haemophilia and HRQoL was conducted. We included only the publications reporting pre- and post-surgery HRQoL data and all orthopedic interventions were considered. Congress abstracts from 2010 were also reviewed. Abstracts and full text articles were screened by two reviewers and conflicts arbitrated. RESULTS: A total of 1,471 articles were retrieved. Following the screening process, 8 full-text articles reporting pre- and post-surgery HRQoL data for patients who received ankle arthrodesis, total knee replacement, ankle replacement or hip arthroplasty were included. Seven studies used patient-reported measures and only one study estimated the EQ-5D using indirect matching techniques. Of the seven studies, four used the visual analogue scale (VAS). Three concluded that post-operative pain was significantly lower and only one study reported that although pain decreased post-surgery, moderate pain remained among patients who underwent multiple joint procedures and received ankle arthrodesis. Of the four studies that reported SF-36/SF-12 scores, significant gains in physical health scores were observed in three and higher mental health scores were reported in one study. Disease-specific measures, Western Ontario and McMaster University (WOMAC) and Oxford Knee Score, were assessed by two studies and improvements in pain and physical functioning were observed on both scales. Evidence from SF-12 summary scores suggests that the improvements in physical functioning are similar for patients with and without inhibitors. CONCLUSIONS: Orthopaedic surgery improves the HRQoL of haemophilia patients with severe arthropathy.