The present study was aimed to develop extended release pellet of Venlafaxine HCL (VEN) employing different tools of Quality by Design (QbD). VEN pellets were prepared by extrusion spheronization technique with the help of L-HPC LH-31 and Hypromellose 15 cps. The pellets were further coated by extended release coating using different ratio of EC 45 cps and Hypromellose 6 cps by fluidized bed process. Based on former knowledge and preliminary experimental data, risk based assessment was done by FMEA and RPN score. For further optimization, 32 full factorial design (FFD) was used for choosing % EC and % coating as independent variables and % drug release at 2, 4, 8, 12 and 20 hrs as dependent variables. Results of DSC study revealed compatibility of VEN with proposed excipients. Statistical analysis and SEG revealed suitability of applied FFD. Results of physicochemical characterization of VEN pellets were in accordance with pharmacopoeia. Drug release from VEN pellets followed Weibull model. Final coating composition of VEN pellets was 8% coat and 84% EC in coating. SEM analysis showed spherical structure of pellets. Short term stability study exhibited stable features of VEN pellets. So, optimized VEN pellets were the promising approach for achieving desirable constant release upto 24 hrs and so choices of design for once a therapy.