Objective To evaluate the instant effects and five-year clinical outcomes of coronary artery disease patients complicated with diabetes mellitus after StentBoost-optimized percutaneous coronary intervention (PCI). Methods From March 2009 to July 2010, 184 patients undergoing PCI at our hospital were found stent underexpansion or malapposition by StentBoost after stents implantation and were divided into the diabetic (n=73, 39.67%) and the non-diabetic group (n=111, 60.33%). All patients received StentBoost-guided post-dilatation after stent implantation. The instant procedural results were measured and clinical outcome after five-year follow-up was analyzed in each group. Between-group comparisons were performed using Chi-square test or Student's t test. Multivariate logistic regression analysis was carried out to reveal the independent predictors for long-term clinical outcomes of StentBoost-optimized PCI . Results After StentBoost-guided post-dilatation, the minimum diameter (MinLD), maximum diameter (MaxLD) and average diameter in both groups increased significantly than before (P<0.001), the (MaxLD-MinLD)/MaxLD ratio and the in-stent residual stenosis decreased accordingly (P<0.001). The five-year follow-up showed similar mortality rate (4.92% vs. 2.86%, P=0.67) and major adverse cardiac event rate (11.48% vs. 11.43%, P = 1.0) between the diabetic and the non-diabetic group, whereas the recurrence of angina pectoris was higher in the diabetic group compared to the non-diabetic group (47.54% vs. 29.52%; P=0.02). A multivariate logistic regression analysis revealed that age and left ventricular ejection fraction rather than diabetes mellitus were independent predictors for long-term clinical outcomes. Conclusions StentBoost could effectively improve instant PCI results; the long-term clinical outcomes of StentBoost-optimized PCI were similar between diabetic and non-diabetic patients. Age and left ventricular ejection fraction were the independent predictors for long-term clinical outcomes.