Small vessel size represents a critical risk factor for an adverse outcome after both conventional balloon angioplasty (POBA) and stenting. Gradual and prolonged balloon angioplasty (GPBA) has been shown to cause less arterial trauma, which results in higher procedural success rates and fewer in-hospital complications than POBA. The aim of this study was to assess the clinical and angiographic benefits of primary GPBA with a perfusion balloon in small coronary arteries, as compared with cutting balloon angioplasty (CBA) and POBA.A total of 263 patients with symptoms and reference diameters 10 minutes in GPBA. Crossover to stent was allowed for inadequate results. Follow-up angiography was performed after 6 months. The primary end point was angiographic restenosis at follow-up.Compared with POBA, GPBA resulted in a lower final residual diameter stenosis (27.3% vs 34.2%, P =.01) and decreased the need for stent placement (8.0% vs 22.2%, P =.031). At follow-up, the restenosis rates were lower with GPBA (31.3%, P =.034) and CBA (32.9%, P =.059) than POBA (50.6%). Target lesion revascularization was less frequently needed with GPBA (20.5%, P =.043) and CBA (20.0%, P =.033) than POBA (37.6%). Additionally, the event-free survival rate was higher with GPBA (77.1%, P =.033) and CBA (76.4%, P =.047) than POBA (58.8%).In small coronary arteries, both GPBA and CBA resulted in favorable angiographic and clinical outcomes. With a lower restenosis rate and target lesion revascularization rate, GPBA may be a superior strategy for small vessels compared with POBA.