We report a facile approach to fabricating electrospun drug-loaded organic/inorganic hybrid nanofibrous system for antibacterial applications. In this study, nano-hydroxyapatite (n-HA) particles loaded with a model drug, amoxicillin (AMX) were dispersed into poly(lactic-co-glycolic acid) (PLGA) solution to form electrospun hybrid nanofibers. The loading of AMX onto n-HA surfaces (AMX/n-HA) and the formation of AMX/n-HA/PLGA composite nanofibers were characterized using different techniques. We show that AMX can be successfully adsorbed onto the n-HA surface and the formed AMX/n-HA/PLGA composite nanofibers have a uniform and smooth morphology with improved mechanical durability. Cell viability assay and cell morphology observation reveal that the formed AMX/n-HA/PLGA composite nanofibers are cytocompatible. Importantly, the loaded AMX within the n-HA/PLGA hybrid nanofibers shows a sustained release profile and a non-compromised activity to inhibit the growth of a model bacterium, Staphylococcus aureus. With the significantly reduced burst-release profile, good cytocompatibility, improved mechanical durability, as well as the remained antibacterial activity, the developed AMX/n-HA/PLGA composite nanofibers should find various potential applications in the fields of tissue engineering and pharmaceutical science. (C) 2012 Elsevier Ltd. All rights reserved.