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Background: Drug-eluting stents have reduced the need of target vessel revascularization (TVR), when compared to bare metal stents. However, some studies have shown increased risk of stent thrombosis with the use of these devices. As a consequence, new drug-eluting stents with biodegradable polymers have been developed to improve results. Methods: The first 100 patients treated with the Biomatrix TM stent from November 2008 to September 2010, were included. Only those with contraindication to dual antiplatelet therapy were excluded. Primary endpoint was the occurrence of major adverse cardiac events in the late follow-up. Results: Mean age was 64 ± 11.7 years, 73% were men, 43% were diabetic and 40% had stable angina. One hundred and sixty-four lesions were treated, 71% of them were complex lesions (B2/C). The vessel reference diameter and the length of lesions were, respectively, 2.79 ± 0.49 mm and 18.3 ± 9.2 mm. Procedure success was 96%. Clinical follow-up data was obtained in 99% of the eligible patients in a mean period of 243 ± 160 days. The primary endpoint rate was 9% (cardiac death 4%, nonfatal myocardial infarction 2%, TVR 3%). Stent thrombosis was observed in 1% of the patients. There was no late or very late thrombosis. Conclusions: In this real world experience, the use of the Biomatrix TM stent showed good results. These findings, together with those available in the literature, provide additional evidences for the use of this stent in the daily clinical practice, including off-label indications.