OBJECTIVE The objective of present study was to develop chitosan-based sustained release nicorandil microspheres to reduce the dosing frequency. METHODS The nicorandil-loaded chitosan microspheres were formulated by emulsion crosslinking method. A 3(2) factorial design was employed to study the influence of drug: Polymer ratio and volume of glutaraldehyde (GA) on percentage entrapment efficiency, particle size, and % drug release at 8 h. RESULTS The entrapment efficiency was found to be 41.67 ± 1.43-77.33 ± 1.97% and particle size range 65.67 ± 2.08-146.67 ± 2.18 μm. The batch CH5 showed 79.11 ± 2.23 and 96.21 ± 2.41% drug release at 8 and 12 h, respectively. CONCLUSIONS DRUG: Polymer ratio and volume of GA had significant effect on % entrapment efficiency, particle size, and % drug release. From the scanning electron microscopy (SEM) study observed that microspheres were spherical and fairly smooth surface. Fickian diffusion was the mode of drug release from nicorandil-loaded chitosan microspheres formulations.