Objective To investigate the influence of the availability of drug eluting stents (DES) on treatment choice (TC) among medical therapy (MT), coronary by-pass surgery (CABG) or percutaneous coronary interventions (PCI) and the consequent clinical outcomes in patients hospitalised because of coronary artery disease (CAD). Design Observational study comparing two cohorts hospitalised immediately before, and 3 years after DES availability. Setting Thirteen hospitals with cardiology facilities. Patients 2131 consecutive patients with at least one coronary stenosis >50% at coronary angiography (CA) after exclusion of those with acute myocardial infarction or previous CABG or associated relevant valvular disease. Main outcome measures Treatment choice after CA and 4-year clinical outcomes. Results TC among MT (27% vs 29.2%), PCI (58.6% vs 55.5%) and CABG (14.5% vs 15.3%) was similar in the DES and bare metal stent (BMS) periods (p = 0.51). At least one DES was implanted in 57% of patients treated with PCI in 2005. After 4 years, no difference in mortality (13.8% vs 13.2%, p = 0.72), hospital admissions for myocardial infarction (6.6% vs 5.2%, p = 0.26), stroke (2.2% vs 1.7%, p = 0.49) and further revascularisations (22.3% vs 19.7%, p = 0.25) were observed in patients enrolled in the DES and BMS periods. Only in patients with Syntax score 23–32 a significant change of TC (p = 0.0002) occurred in the DES versus BMS period: MT in 17.4% vs 31%, PCI in 62.2% vs 35.8%, CABG in 20.3% vs 33.2%, with similar 4-year combined end-point of mortality, stroke, myocardial infarction and further revascularisations (45.3% vs 34.2%, p = 0.087). Conclusions Three years after DES availability, the TC in patients with CAD has not changed significantly as well as the 4-year incidence of death, myocardial infarction, stroke and further revascularisations. In subgroup with Syntax score 23–32, a significant increase of indications to PCI was observed in the DES period, without any improvement of the 4-year clinical outcome.