Background: The obesity paradox has been recently proposed in various heart disease treatments including percutaneous coronary intervention. However, no study has yet examined the effect of the obesity paradox on patients with diabetes mellitus (DM). Our aim was to evaluate the impact of body mass index (BMI) on the mid-term restenosis rate of sirolimus-eluting stent (SES) implantation in patients with and without DM. Furthermore, we evaluated the differences between de novo and in-stent restenosis lesions. Methods: We evaluated 2,949 patients, 1211 (41.0%) of whom had had DM and had undergone SES implantation (excluding hemodialysis patients and hybrid stenting) between November 2002 and December 2008. The patients were classified as under/ normal weight (BMI 25) and overweight (BMI 25). We compared the restenosis rates with SES within 8 months between de novo and in-stent restenosis lesions based on BMI and the presence or absence of DM. Results: Among patients with DM, the group of BMI 25 (439 patients) had significantly reduced restenosis rate than that of BMI 25 (577 patients) in de novo lesions (BMI 25, 13.1%; BMI 25, 7.8%; p 0.001), whereas no significant difference was present between the two BMI groups in in-stent restenosis lesions (BMI 25, 19.4%; BMI 25, 16.5%; p 0.981). In contrast, among patients without DM, there was no significant difference in the restenosis rates between the two BMI groups in both de novo lesions (BMI 25, 6.1%; BMI 25, 5.3%; p 0.433) and in-stent lesions (BMI 25, 14.6%; BMI 25, 14.5%; p 0.535). Conclusions: The obesity paradox was present only in restenosis after SES implantation for de novo lesions in patients with DM.