Objectives. This study sought to examine the mechanism of increasing coronary flow reserve after balloon angioplasty and stenting. Background. Coronary vasodilatory reserve (CVR) does not improve after percutaneous transluminal coronary angioplasty in ≤50% of patients, postulated to be due to impaired microvascular circulation or inadequate lumen expansion despite adequate angiographic results. Methods. To demonstrate the role of coronary lumen expansion, serial coronary flow velocity (0.014-in. Doppler guide wire) was measured in 42 patients before and after balloon angioplasty and again after stent placement. A subset (n = 17) also underwent intravascular ultrasound (IVUS) imaging of the target sites after angioplasty and stenting. CVR (velocity) was computed as the ratio of adenosine-induced maximal hyperemic to basal average peak velocity. Results. The percent diameter stenosis decreased from (mean ± SD) 84 ±13% to 37 ± 18% after angioplasty and to 8 ± 8% after stenting (both p < 0.05). CVR was minimally changed from 1.70 ± 0.79 at baseline to 1.89 ± 0.56 (p = NS) after angioplasty but increased to 2.49 ± 0.68 after stent placement (p < 0.01 vs. before and after angioplasty). IVUS lumen cross-sectional area was significantly larger after stenting than after angioplasty (8.39 ± 2.09 vs. 5.10 ±2.03 mm2, p < 0.05). Anatomic variables were related to increasing coronary flow velocity reserve (CVR vs. IVUS lumen area: r = 0.47, p < 0.005; CVR vs. quantitative coronary angiographic percent area stenosis: r = 0.58, p < 0.0001). Conclusions. In most cases, increases in CVR were associated with increases in coronary lumen cross-sectional area. These data suggest that impaired CVR after angioplasty is often related to the degree of residual narrowing, which at times may not be appreciated by angiography. A physiologically complemented approach to balloon angioplasty may improve procedural outcome.