This work is based on formulating and optimizing controlled release (CR) valsartan (160 mg) tablets using different viscosity grades of the cellulosic polymer. The objective was to develop an effective once-daily drug delivery system of this cardiovascular agent. Central composite design was used for designing the formulations. Polymers used were Methocel(R) K4M, K15M and K100M. Compatibility of excipients with active was studied through FT-IR. Micromeritic properties were determined and formulations exhibiting appropriate flow characteristics were compressed. Swelling behavior and in vitro buoyancy effect were studied and response surface curves were constructed to optimize the formulation. Multi-point dissolution profiles of valsartan CR tablets at pH 1.2, 4.5 and 6.8 were obtained. Model-dependent and model-independent methods were performed including f(2), stability test as per ICH guidelines and ANOVA. FT-IR studies revealed the compatibility of valsartan with all excipients. Formulation K4T9 (containing 25% K4M polymer) was selected to be the best optimized trial, based on physical properties and controlled release profile (23% at 4 h, 82% at 16 h and 100% at 24 h). Results of buoyancy and swelling behavior indicated that HPMC-K4M polymer exhibited excellent floating lag time and swelling indexes. In vitro drug release kinetics showed that formulation K4T9 displayed Korsmeyer-Peppas drug release pattern with r value > 0.99. The manufacturing process of K4T9 was also found to be reproducible with a shelf life period of 41 and 36 months at room temperature and accelerated conditions, respectively. Valsartan CR matrix-based formulation was successfully prepared with Methocel K4M retardant.