The sustained release matrix dosage type is favored to prevent blood level variations found in the Dipyridamole drug. The goal of this research was to formulate Dipyridamole's sustained release matrix tablet, Dipyridamole is a thromboembolic risk preventive drug for heart valve replacement and long-term angina pectoris treatment will be well absorbed in the stomach. Maintaining long-term therapeutic plasma concentration and increasing bioavailability by using various polymers to improve bioavailability and to minimize the dosing rate and side effects by integrating a 3-factor, 3-level Box-Behnken statistical design of surface response technique. Sustain release polymers such as HPMC K4M (X1), MCC 101 (X2) and Magnesium Stearate (X3) are the dependent variables and Independent variable is the percentage release of drug at 12 h (Y1) were determined. Response surface plots of Box-Behnken design have been drawn, quadratic models have been statistically validated and optimized formulations have been selected Based on grid search and feasibility. The physical evaluation, drug content and % drug release tests were conducted on all the 13 box Behnken design runs. Zero order, first order, Higuchi and Korsemayer-peppas in terms of r2 and n-value were generated using various release kinetic models and equations. The response surface plots showed high degree of prediction. The desired batch depicted a steady and sustained release from the confirmatory runs (best fit model– Higuchi model (n=0.9862). Hence, the bioavailability of Dipyridamole cocrystal sustained release matrix tablets was increased using response surface designs.