The traditional method for obtaining best combination of reaction parameters for graft copolymerization of 4-vinylpyridine onto poly(vinylidene fluoride) films was modified using Box-Behnken factorial design available in the response surface method (RSM). A computer-assisted statistical simulator was used to obtain the optimum absorbed dose, monomer concentration, grafting time and reaction temperature to achieve the highest degree of grafting (G%) based a quadratic model. The validity of the developed model was confirmed by experimental data, which only deviated by a 2% from the predicted value of G% confirming the effectiveness of RSM in optimization of the reaction parameters in the present grafting system. A comparison was also made between the obtained model and that of 1-vinylimidazole/poly(ethylene-co-tetrafluoroethylene) grafting system. The chemical structure, morphology and thermal stability of the obtained graft copolymers was investigated by means of Fourier transform infrared, filed emission scanning electron microscope, and thermogravimetric analysis, respectively. (c) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 127: 1659-1666, 2013