Summary. Evidence suggests greater doses of recombinant activated factor VII (rFVIIa; NovoSeven®, Novo Nordisk A/S, Bagsværd, Denmark) than currently administered may result in enhanced haemostasis and convenience for patients with haemophilia A and B with inhibitors. This study evaluated efficacy and safety of rFVIIa and an activated prothrombin complex concentrate (APCC; Factor Eight Inhibitor Bypassing Activity [FEIBA]®, Baxter AG, Vienna, Austria) for controlling joint bleeds in a home-treatment setting. Patients received each of three treatments in one of six possible sequences: 270 μg kg−1 rFVIIa at hour 0 + placebo at hours 3 and 6, 90 μg kg−1 rFVIIa at hours 0, 3 and 6, and 75 U kg−1 APCC at hour 0. Efficacy was assessed by the requirement for additional haemostatics within 9 h and by a novel global response algorithm. The percentage of rFVIIa 270 μg kg−1 group patients requiring additional haemostatics within 9 h (8.3%) was significantly lower than that for the APCC group (36.4%, P = 0.032). The percentage of rFVIIa 90 × 3 μg kg−1 group patients requiring such rescue medication (9.1%) was also lower compared to the APCC group. This result approached, but did not reach statistical significance (P = 0.069). Both rFVIIa treatment groups showed similar use of rescue medication (8.3% and 9.1% of episodes for rFVIIa 270 μg kg−1 and rFVIIa 90 × 3 μg kg−1 groups respectively). No significant differences in treatment response were observed with the global response algorithm (P = 0.173). No safety issues were identified. A single dose of rFVIIa 270 μg kg−1 is as safe and effective as rFVIIa 90 × 3 μg kg−1 dosing, and may be considered a potentially more effective alternative to APCCs for the management of joint bleeding in this population.