Objective To investigate effects from the protrusion height of drug-eluting stent (DES) on kinetics of drug release and hemodynamics, so as to provide references for the optimization of DES design. Methods Based on computational fluid dynamics (CFD), coupling analysis on kinetics of drug release and hemodynamics was conducted by studying three stent models with different protrusion height to numerically investigate the distribution of drug concentration and wall shear stress. Results The increase in protrusion height of the stent was beneficial to the drug deposition; however, it could also increase the length in the low shear stress area. Comparatively, the increase percentage of drug concentration with the increasing protrusion height was remarkably less than that of the increasing length in low shear stress area. Conclusions By comprehensive consideration of both the drug concentration and wall shear stress, lower protrusion height is recommended for DES so as to effectively reduce the risk of restenosis.