Sustained release cellulose acetate (CA) and ethyl cellulose (EC) polymer blend nanofibers loaded with ketoprofen (KET) were successfully prepared by electrospinning. Successful fiber formation has been investigated by using two different binary solvent systems, i.e., acetic acid + distilled water (2:1 v/v) and acetone + N,N-DMAc + ethanol (2:1:1 v/v). Scanning electron microscopy (SEM) images showed that morphological features gradually change as the ratio of both polymers change. Nanofiber diameter also decreases as the CA content is increased in the polymer blend solution from 77.25 +/- 27 to 72.39 +/- 30 nm. Drug release profiles were evaluated by in-vitro drug release experiments. Drug release follows a pseudo-Fickian behavior of diffusion and shows a sustained release mechanism. Nanofibers containing more CA show greater controlled release capacity as compared to EC. X-ray diffraction (XRD) patterns of CA and EC polymer blend nanocomposites show that crystalline ketoprofen has changed into an amorphous state. Fourier transform Infrared (FTIR) analysis indicates hydrogen bonding occurs between the drug and the polymer, accounting for molecular integration of the two components. The thermal stability of the prepared polymer blend was also studied using thermo-gravimetric analysis (TGA). A polymer blend sustained release drug delivery system prepared by electrospinning make it possible to fabricate other novel drug releasing systems.