Objectives: Aorto-ostial lesions (AOL) are technically challenging, given their greater propensity to be calcific and associated with elastic recoil compared to non-ostial lesions. This study set out to assess angiographic and clinical outcomes in patients with AOL treated using either paclitaxel-eluting stents (PES) or sirolimus-eluting stents (SES) compared to bare-metal stent (BMS) implantation. Methods: We retrospectively identified 175 consecutive patients with 175 AOL involving the left main, right coronary artery or bypass graft. PES, SES and BMS were implanted in 69, 50 and 56 patients, respectively. Results: Angiographic and procedural success was 100 and 97.1% for PES, 100 and 94% for SES, and 100 and 94.6% for BMS, respectively (p not significant). At 12 months, the rates of target lesion (8.7% for PES, 4.0% for SES) and target vessel revascularization (3.0% for PES, 8.0% for SES) were significantly lower in the drug-eluting stent group compared to BMS (32.1 and 35.7%, respectively). There was no difference in the rate of death/MI in the BMS versus drug-eluting stent groups (5.4 vs. 2.4%, p = 0.32). Conclusions: In the treatment of AOL, drug-eluting stents reduce the need for repeat revascularization at 12 month follow-up compared to BMS, with no difference in mortality or MI rate.