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Introduction: Intra‐articular platelet‐rich plasma (PRP) injection therapy has been extensively applied in clinical practice to treat musculoskeletal disorders such as osteoarthritis, but the treatment for haemophilic arthropathy is rarely reported. Aims: This study aimed to compare the efficacy of intra‐articular PRP vs hyaluronic acid (HA) injections in treating haemophilic arthropathy of knee joints. Patients: Twenty‐two haemophilia patients (mean age, 41.1 ± 1.7 [range, 20‐50] years) with painful haemophilic arthropathy of the knee were enrolled for this open‐label and observer‐blind study. Methods: Eleven patients were treated with a single intra‐articular injection of PRP and the other 11 received five consecutively weekly intra‐articular injections of HA. Outcome assessment included pain by visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Chinese Version and synovial change determined by ultrasonography. Results: Platelet‐rich plasma and HA intra‐articular injection showed statistically significant reduction in VAS, WOMAC total score and hyperaemia score from baseline to 6‐month post‐treatment. Inter‐group comparison showed statistically significant difference in the change in VAS score, WOMAC pain score, physical function score and total score at 6 months, wherein PRP group showed sustained beneficial effect than HA group at 6 months. Conclusion: Our study demonstrates that, in comparison with five weekly injections of HA, a single PRP injection resulted in better improvement in pain relief and knee joint function, and greater reduction in synovial hyperaemia for up to 6 months. Our results suggest that PRP may be practical and effective for haemophilic knee arthropathy, and further investigation is warranted. [ABSTRACT FROM AUTHOR]