Summary. Finding differences in drug utilization patterns within rare patient populations is challenging without access to a large sample. Our objective was to identify patient and treatment-related factors associated with differences in annual recombinant factor VIII (rFVIII) utilization in a large cohort of haemophilia A patients. This retrospective analysis utilized a large, US specialty pharmacy dispensing database from January 2006 to September 2009. Differences in median annual FVIII utilization (IU kg−1year−1) by age, severity, treatment regimen, rFVIII product type and health insurance plan were tested using non-parametric statistics and regression analysis. A total of 1011 haemophilia A patients were included in the overall analysis. Severe haemophilia patients had higher median annual FVIII utilization than mild/moderate patients (P < 0.0001). Median annual FVIII utilization was also significantly different between treatment regimens (episodic = 1429 IU kg−1year−1 vs. prophylaxis = 3993 IU kg−1year−1 for severe patients, P < 0.0001). Children (0–12 years old), adolescents (13–18 years old) and adults (19+ years old) with severe haemophilia A receiving prophylaxis utilized 4588, 4082 and 3223 IU kg−1year−1 (P < 0.0001). After controlling for age, severity, treatment regimen and insurance type, regression analysis revealed B domain-deleted recombinant FVIII (BDD-rFVIII) was associated with 33% higher FVIII consumption compared with full-length recombinant FVIII (FL-rFVIII) (P = 0.0172). Similar results were also seen when matching BDD-rFVIII and FL-rFVIII patients. Health insurance type was not associated with annual FVIII utilization. As expected, age, severity and treatment regimen were significantly associated with FVIII utilization. After controlling for confounders, patients receiving FL-rFVIII prophylactically were associated with lower annual FVIII utilization compared with patients receiving BDD-rFVIII prophylactically.