Abstract: AIM:To investigate the effects of different implantation modes of drug-eluting stents upon restenosis of small vessel lesions (diameter ≤2.75 mm). METHODS: Sixty-nine patients (51 males and 18 females) with 111 lesions were enrolled after implanting drug-eluting stents. The experimental group consisted of direct implantation of drug-eluting stents and the 64 stents included 53 rapamycin and 11 paclitaxel drug-eluting stents. The control group consisted of implanted drug-eluting stents after balloon predilation and the 47 stents included 41 rapamycin and six paclitaxel drug-eluting stents. After procedures, coronary angiography and intravascular ultrasound (IVUS) were performed immediately in case of chest pain. For those without chest pain, coronary angiography and IVUS were performed after 6 months. In-stent restenosis was detected by IVUS and the rates of in-stent restenosis were compared between groups. RESULTS: The average diameters of small vessels immediately evaluated postoperatively in experimental group and control group were, respectively (2.38±0.26)mm and (2.34±0.24)mm (P>0.05). The average cross-sectional areas of lumens of small vessels in experimental group and control group were, respectively, (0.26±0.30) mm2 and (4.3±0.9) mm2 (P>0.05). However, 6 months postoperatively, the loss of lumens in experimental group and control group were (1.44±0.30) mm and (0.98±0.24) mm, respectively (P=0.01) and the ratios of in-stent restenosis were 14.60% and 29.78%, respectively (P<0.05). CONCLUSION: For patients with small vessel lesions, direct implantation of drug-eluting stents is superior to implanting drug-eluting stents after balloon predilation.