OBJECTIVE: To compare the rate of restenosis between a cardiac rehabilitation (CR) group and a control group within three different generations of drug eluting stents (DES). METHOD: Patients who received DES due to an acute coronary syndrome were included. They were divided into a CR group and a control group. The CR group received six to eight weeks of early cardiac rehabilitation program in a hospital setting, and sustained a self-exercise program for six months in a community. The control group was instructed to exercise by themselves after leaving the hospital. Nine months after the first onset of disease, we implemented a coronary angiography and compared the two groups. In addition, we divided the patients into three subgroups according to the generation of DES, and compared the rate of restenosis between the CR group and control group within these three subgroups. RESULTS: At 9 months, in-stent restenosis, measured as an in-segment late luminal loss (LLL) of the stented coronary area, was smaller in the CR group (n=52) 0.16+/-0.42 mm compared to the control group (n=51) 0.39+/-0.78 mm (p<0.05). A reduction of LLL in the CR group compared to the control group was consistent among the three different generations of DES. CONCLUSION: The CR program is strongly associated with a significant reduction in LLL in the stented coronary segments, regardless of the generation of DES.