Self-microemulsifying drug delivery system (SMEDDS) is an important strategy to enhance solubility and bioavailability of drugs having low aqueous solubility. Dipyridamole is BCS class II drug which suffers from poor solubility and bioavailability. The present work was undertaken to improve the solubility of dipyridamole by formulating SMEDDS. The solubility of dipyridamole was estimated in various oils, surfactants, and cosurfactants. Pseudoternary phase diagram was developed by water titration method to select the surfactant to cosurfactant ratio (Smix ratio). Liquid SMEDDS was prepared using selected combination of oil, surfactant, and cosurfactant and different parameters were evaluated to select optimized combination. Results revealed that castor oil in which drug solubility was greater and 1:2 Smix ratio was used for the development of various liquid SMEDDS formulation. Thus, due to the fast emulsification, higher drug content, thermodynamic stability, and percent transmittance S5 formulation containing 60% castor oil and 40 % Smix (1:2 ratio) was selected optimized and further investigated. The average droplet size of the optimized S5 formulation after dilution with distilled water was obtained 160.2±3.6 nm and displayed Gaussian distribution. Moreover, lower value of PDI that is 0.324 indicated uniformity of the globule size in the microemulsion formed. The S5 formulation possessed zeta potential of -23.1 mv indicating the stability of the formulation. The results of transmission electron microscopy revealed spherical shape of microemulsion droplets. Hence, liquid SMEDDS of dipyridamole can be employed to modify the solubility and bioavailability of dipyridamole having inadequate water solubility