Patients with haemophilia requires different amounts of FVIII to prevent and treat bleeds. We hypothesise that this is because FVIII has variable effects on individual patients’ global haemostasis. Twelve patients with severe haemophilia A were infused with 50 IU/kg FVIII and thrombin generation in platelet rich (PRP) and platelet poor plasma (PPP) and velocity of changing clot elasticity were measured preinfusion and at nine subsequent time points over 72 h. Despite a close correlation between median FVIII and median initial rate of thrombin generation (R² 0·94), endogenous thrombin potential (ETP; R² 0·94) and peak thrombin (R² 0·91) in PPP, there was wide inter‐patient variability at each time point. There was, however, a highly predictable intra‐patient relationship between FVIII level and thrombin generation. Inter‐patient variability was due to both differences in FVIII levels and the variable effect FVIII had on an individuals’ thrombin generation. The utility of PRP was limited because, at low‐FVIII levels, only rate of thrombin generation was measurable. At low‐FVIII concentrations, the rate of thrombin generation in PPP was the most useful test whilst at higher levels ETP and peak thrombin could also be used.