Objective: To assess immediate and mid-term clinical and angiographic outcomes of the dexamethasone drug-eluting stent (D-DES) in patients with acute coronary syndrome (ACS). Patients and methods: A prospective, nationwide, controlled, registry. Inflammation plays a key role in ACS, and the anti-inflammatory effects of local elution of dexamethasone in unstable plaques may represent a valid therapeutic approach. All patients had ACS on admission (n = 332). 81.5% of the patients had unstable angina and 18.5% had non-ST elevation myocardial infarction (MI). 47% had ST-T segment changes, 59% had troponin elevation, 77% had elevated C-reactive protein levels and 48% had intermediate-high Thrombolysis in Myocardial Infarction risk score. Patients were treated according to an early invasive approach with 420 D-DES in 387 coronary lesions. Primary end point was the cumulative incidence of death, MI and ischaemia-driven target vessel revascularisation (TVR) at 6 months. Results: At 30 days, 2 (0.6%) patients died, and sub-acute stent thrombosis occurred in 2 patients. At 6 months, 328 (98.8%) patients were controlled, 3 (0.9%) patients had died, 7 (2.1%) had MI and 28 (8.5%) underwent ischaemia-driven TVR. Therefore, the primary end point occurred in 11.5% of patients. At multivariate analysis, multi-vessel coronary artery disease (odds ratio (OR) = 2.16, 95% CI = 1.47 to 3.17, p = 0.0001) and vessel diameter (2.75 mm (OR = 1.64, 95% CI = 1.08 to 2.49, p = 0.02) were independent predictors of 6-month clinical events. Global angiographic restenosis rate was 33.3%. Conclusion: This is the first large, multicentre analysis of the clinical and angiographic outcomes obtained with D-DES implanted in ACS. D-DES offers a low rate of clinical events at 6 months, but has no antirestenosis effect.A n ''early-invasive approach'' for the treatment of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is superior to a conservative strategy in patients with either ST-segment depression, troponin elevation or other high-risk indicators. However, recurrence of ischaemia at mid-term in this setting was as high as 22-32.3% in the landmark FRagmin during InStability in Coronary artery disease (FRISC) study and Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction 18 (TACTICS-TIMI) study. Recently, the high efficacy of drug-eluting stents (DES) in reducing restenosis has been confirmed in a subgroup of patients with NSTE-ACS enrolled in randomised studies not designed, however, to assess the performance of these stents in this specific clinical setting. Inflammation plays a predominant role in the cellular mechanisms of unstable plaque. The evolution either towards plaque passivation, healing and stabilisation or towards plaque rupture and the occurrence of major adverse cardiac events (MACE) is influenced by inflammatory mechanisms. Local elution of anti-inflammatory agents is the rationale for the use of D-DES in these patients. This...