Directional atherectomy removes plaque in a targeted portion of a vessel wall. In practice, orienting the cutter toward maximal plaque accumulation and assessing the depth of vessel excision is difficult with angiographic guidance alone. Accordingly, we designed and tested a prototype catheter that combines ultrasound imaging capability with directional atherectomy in a single device. Twenty-seven in vitro vessels (32 lesions) were treated with atherectomy alone or with atherectomy combined with ultrasound. Lesion characteristics before and after the procedure were similar in each group. A significant decrease in the incidence of subintimal tissue excision was observed in the atherectomy-ultrasound group (21.1%) compared to the group that had debulking with atherectomy alone (54.5%). In addition, among specimens with media and/or adventitia the relative amount of subintimal tissue was significantly less (p < 0.001) with ultrasound guidance than with atherectomy alone (11.2% +/- 10.1% vs 34.2% +/- 8.5%). We conclude that ultrasound-guided directional atherectomy is technically feasible and may aid in achieving maximal plaque debulking and reduce the amount of subintimal injury.