Sirolimus-loaded bi-layer polymer matrices were fabricated and the effects of sirolimus release on proliferation and viability of human coronary artery smooth muscle cells (cSMCs) were investigated. Human cSMC recovery after sirolimus treatment and the attachment of human cSMC to sirolimus-eluting films were also studied. It was found that the released sirolimus inhibited growth factor stimulated human cSMC proliferation successfully. However, different drug doses appeared to have the same effect in the extent of inhibition of proliferation in this study. Cell viability was also observed to decrease with the presence of sirolimus and the attachment to sirolimus-eluting films was inhibited. The recovery of human cSMCs was found to be related to the duration of inhibition time by sirolimus. Longer inhibition resulted in a slower recovery, which suggests that sustained release is more effective than rapid release of a higher amount in the inhibition of cSMC proliferation. This observation may be important for the design of a drug-eluting stent.