Objectives. The objective of this study was to determine the feasibility, safety and outcome of deferring angioplasty in patients with angiographically intermediate lesions that are found not to limit flow, as determined by direct translesional hemodynamic assessment. Background. The clinical importance of some coronary stenoses of intermediate angiographic severity frequently requires noninvasive stress testing. Direct translesional pressure and flow measurements may assist in clinical decision making in patients with such stenoses. Methods. Translesional spectral flow velocity (Doppler guide wire) and pressure data were obtained in 88 patients for 100 lesions (26 single-vessel and 74 multivessel coronary artery lesions) with quantitative angiographic coronary narrowings (mean ± SD diameter narrowing 54 ± 7% [range 40% to 74%]). Target lesion angioplasty was prospectively deferred on the basis of predetermined normal values, defined as a proximal/distal velocity ratio < 1.7 or a pressure gradient <25 mm Hg, or both. Patients were followed up for 9 ± 5 months (range 6 to 30). Results. In the deferred angioplasty group, translesional velocity ratios were similar to those of a normal reference group (mean 1.1 ± 0.32 vs. 1.3 ± 0.55) and significantly lower than those of a reference cohort of patients who had undergone angioplasty (2.27 ± 1.2, p < 0.05). The mean translesional pressure gradient in the deferred angioplasty group was also lower than that in the angioplasty group (10 ± 9 vs. 45 ± 22 mm Hg, p < 0.001). At follow-up in the deferred angioplasty group, four, six, zero and two patients, respectively, had had subsequent angioplasty, coronary artery bypass graft surgery or myocardial infarction or had died. In one patient, death was related to angioplasty of a nontarget artery lesion, and one patient with multivessel disease had a cardiac arrest due to ventricular fibrillation 12 months after lesion assessment. Among the 10 patients requiring later angioplasty or coronary artery bypass grafting, only six procedures were performed on target arteries. No patient had a complication of translesional flow or pressure measurements. Conclusions. These data demonstrate the safety, feasibility and clinical outcome of deferring angioplasty of coronary artery narrowings associated with normal translesional coronary hemodynamic variables. Given the practice of performing angioplasty without ischemic testing or when testing is inconclusive, translesional hemodynamic data obtained at diagnostic catheterization can identify patients in whom it is safe to postpone angioplasty.