Summary Objectives We determined the effect of two-time inflation of the stent balloon on stent expansion and its responsible factor. Methods Subjects included 61 patients with de novo coronary artery lesions, in whom 12 sirolimus-eluting, 27 paclitaxel-eluting, and 22 other stents were deployed twice at identical inflation pressures (11.3±2.3atm) and inflation times (5, 10, 20, and 40s). After the first and second deployments, minimum lumen diameter (MLD), minimum lumen area (MLA), and distensibility index (DI) were determined using intravascular ultrasound. Results After the second inflation, MLA was significantly increased (5s: 12.9%, 10s: 14.5%, 20s: 9.4%, 40s: 9.5%). MLD and DI were also significantly increased. In the single and double inflation groups, DI in each group was significantly correlated with inflation time (single: r=0.409, double: r=0.351). DI was not significantly different between double 5-s and single 10-s inflations, between double 10-s and single 20-s inflations, or between double 20-s and single 40-s inflations. Additional stent balloon inflation by higher pressure in 30% and another balloon in 18% of the patients were required. Conclusions Two-time stent balloon inflation may allow better stent expansion regardless of inflation time and two-time inflation may be equivalent to longer inflation.