The objective of this work was to develop multi layered matrix sustained release tablets of highly water soluble Venlafaxine hydrochloride using natural gums (HPMC K-100M and Xanthan gum). The tablets containing Venlafaxine hydrochloride 150 mg were prepared using hybrid wet granulation barrier layer technology, using Xanthan gum and HPMC K 100M as rate controlling ingredient in the middle layer and Xanthan gum in the barrier layers. After evaluation of physical characteristics of tablets, the dissolution studies were performed in 900 ml of distil water at 100 rpm using the USP XXIII basket apparatus up to 24 hrs. The triple layer tablet gives the release pattern similar to reference product. The radar diagram, similarity factor f2 were used to evaluate the similarity of test product with the reference product. The multi layered matrix tablets overcome the problem of nonlinearity associated with diffusion controlled matrix devices by reducing the surface area of drug containing layer exposed to dissolution medium. Different dissolution models were applied to the drug release data of the optimized batch to evaluate release mechanism and kinetics .Drug release kinetic of the optimized triple layered tablets best fits to Higuchi model where as the release exponent value obtained for Korsmeymer Peppas model was less than 0.45, which is beyond the limit of the model. Release mechanism appears to be complex mechanism of swelling, diffusion, erosion and barrier controlled.