For hemophilia A, factor VIII (FVIII) replacement is still the standard of care for both acute bleeding episodes and prophylaxis. While plasma-derived FVIII products are still available, approximately 75% of the hemophilia community uses recombinant human FVIII products (rhFVIII). However, due to its large molecular weight and complicated post-translational modification, rhFVIII remains as one of the most challenging therapeutic proteins to produce, which leads to the unnecessarily high costs for vulnerable patients and their families. To address this issue, we recently explored if von Willebrand factor (vWF) chaperone would enhance the rhFVIII expression by co-expressing a B-domain–deleted (BDD) rhFVIII and a modified vWF fragment. Using this approach, an unexpectedly high yield (>2000IU/ml) of rhFVIII was achieved in lab-scale culture as well as in large-scale production (200L). The purified rhFVIII displayed similar molecular characteristics to commercial rhFVIII products including thrombin cleavage, glycosylation, tyrosine sulfation and binding affinity to vWF. This production platform has also been used successfully for recombinant porcine FVIII and for a new, long-acting FVIII in development. We believe that, using this platform, rhFVIII can become economically competitive and will have a major impact on hemophilia A prophylaxis and on-demand therapy once the product is on the market.