Recombinant human growth hormone (rhGH) has been used clinically for several decades. However, rhGH has a short half-life in vivo and therefore for efficacy requires frequent subcutaneous injection, leading to pain and poor patient compliance. An effective rhGH delivery system able to continuously release rhGH over a comparatively long period (generally over a month) would be a significant clinical advance. In this study, a novel long-duration release strategy of rhGH was developed by encapsulating sugar glass-stabilized rhGH in electrospun, bioresorbable poly(ester urea) (PEU) nanofibers. The rhGH was found to be randomly dispersed among the fibers, and sustained rhGH release with only a modest burst was observed for at least 6 weeks as studied by a bicinchoninic acid (BCA) protein assay. Significantly, the released rhGH remained bioavailable and bioactive as determined by an Nb2 cell bioassay specific for rhGH. Our results suggest the feasibility of this system as an effective long-term sustained release strategy for rhGH and potentially other therapeutic proteins.