The present study was an attempt to develop microspheres for diltiazem HCl using three different polymers. Diltiazem HCl, being a hydrophilic drug was entrapped in the microspheres by w/o solvent evaporation method. To optimize the weight of polymer, totally five batches were prepared for each of the polymer and various evaluation parameters were studied. The ratio 1:2 (i.e. formulation ERS4) shows highest production yield, drug content and percentage entrapment among the all formulations. FTIR and XRD analysis was also carried out for pure drug and drug containing ethylcellulose, eudragit RS 100 and eudragit RL 100 microspheres, which shows there were no drug-polymer interaction. Based on these test, ERS4 was chosen as the best formulation. Then for all the formulations, in vitro release study was carried out for eight hrs. Which shows the formulation ERS4 and ERS5 having much prolonged release compare to remaining formulations. Dissolution data were fitted to different mathematical models, which follows the diffusion controlled release mechanism from all prepared batches.