Controlled release tablets of venlafaxine to be taken at a dosing interval of 12 hours were formulated with venlafaxine hydrochloride (VFH) equivalent to 75 mg of venlafaxine base. Controlled Porosity osmotic pump (CPOP) based drug delivery system was selected for controlled release of venlafaxine. Target release profile, calculated from pharmacokinetic data, was selected and different variables were optimized to achieve the same. The effect of different formulation variables, namely, relative amount of drug to osmogent, coat depth of semi permeable membrane, type of plasticizer and type and level of pore former on the in-vitro release was studied. Cellulose acetate (CA 398-10) was used as the semipermeable membrane. It was found that drug release rate increased with the amount of osmogent because of the increased water uptake, and hence increased driving force for drug release. VFH release was inversely proportional to the thickness of semipermeable membrane; however, directly related to the level of pore former in the membrane. This system was found to deliver VFH at a zero-order rate for 12 hours. Drug release from the developed formulations was free of pH and agitational intensity, but was dependent on the osmotic pressure of the release media. Results of scanning electron microscope studies showed the formation of pores in the membrane from where the drug release occurred. The numbers of pores were directly proportional to the initial level of pore former in the membrane. The in-vitro results of the developed formulations were compared with performance of standard marketed formulation of VFH. The optimized formulation was subjected to stability studies at different temperature and humidity conditions as per ICH guidelines. The superposition method was used to predict steady state plasma levels of VFH after administration of a test dose (75 mg) of optimized formulation.