Percutaneous coronary interventions (PCIs) in diabetic patients with small reference diameter vessels remain an important challenge in interventional cardiology because it is associated with increased complications and restenosis rates. Plain old balloon angioplasty (POBA) has limited efficacy in patients with lesions in small vessels. Although coronary stenting (stent) has been demonstrated to improve both immediate and long-term results after coronary intervention, small reference diameter is a strong predictor of restenosis after stent implantation. Thus, the question of how to best treat diabetic patients with lesions in small reference diameter remains unanswered. The purpose of this international and multicenter study was to compare the incidence of angiographic restenosis between percutaneous transluminal coronary angioplasty (PTCA) and stent in diabetic patients undergoing PCI of small reference diameter vessels using a specially designed phosphoryl choline (PC)-coated stent for small vessels. The patient population comprised of 220 diabetic patients with lesions in small reference diameter (< 2.9 mm but > 2.0 mm) that were randomized into two different PCI strategies: PTCA with provisional stenting (n = 109) versus stent (n = 111). In the PTCA arm, 26 patients (24%) crossed over to stent during the initial procedure; glycoproteins IIb to IIIa was used in 40.5% of patients in both groups. During initial procedure and at 30 days, both strategies of revascularitation had similar clinical success and acute complications. During long-term follow-up, even though requirements of target vessel revascularization and incidence of major adverse cardiovascular event were similar with both techniques, angiographic binary restenosis (45% with PTCA and 28% with stents, P = .047), net gain (0.74 mm with POBA and 0.94 mm with stents, P = .008), and freedom from target vessel failure (66% with POBA and 81.2% with stents, P = .013) were significantly improved when diabetic patients were initially treated with stent therapy. In summary, in diabetic patients with small coronary arteries, the use of a coronary PC coated stent as a primary device during percutaneous interventions was associated with better angiographic and long-term outcome.