In this study, electrospun composite nanofibers containing nanoparticles for the programmable release of dual drugs were successfully fabricated through a one-step, single-nozzle electrospinning technique. Field-emission scanning electron microscopy and scanning electron microscopy were used to examine the morphology of the nanoparticles and electrospun nanofibers, respectively. The distribution of nanoparticles in the composite nanofibers was evaluated by fluorescence microscopy and laser scanning confocal microscopy. The results indicate that the nanoparticles were encapsulated within the composite nanofibers, forming a core-sheath structure. The different release behaviors of the drugs were ascribed to their varying distribution in the nanofibers and their interaction with carriers. A programmable release of both drugs was also achieved by adjusting the preparation process of the electrospinning solution. Composite nanofibers that can provide a platform for dual-drug loading and the programmed release of each drug may find application in drug delivery systems or in the tissue-engineering field. Polymer Journal (2011) 43, 478-483; doi:10.1038/pj.2011.11; published online 2 March 2011