We performed a clinical trial to evaluate the safety and efficacy of a unique lensed-fiber delivery system with a pulsed Neodymium-yttrium aluminum garnet (Nd-YAG) laser in patients with atherosclerotic peripheral vascular disease. The lensed-fiber consists of a spherical silica lens, 1.5 mm in diameter, mounted at the distal tip of a 300 μm silica optical fiber. The Nd-YAG laser is pulsed at 10 Hz, and we delivered 0.5 J/pulse with a pulse duration of 100 msecs in 2- to 5-second bursts. Successful recanalization of stenoses or occlusions was obtained in 9 of 10 patients and was manifested by improvement in blood flow as measured angiographically and with ankle-brachial blood pressure index improvement (> 0.15). There were no arterial perforations or dissections associated with the laser angioplasty. All successfully recanalized patients required adjunctive balloon angioplasty to obtain a satisfactory reduction in luminal diameter stenosis of the treated artery. We conclude that this unique delivery system and the pulsed Nd-YAG laser are a safe and effective method of recanalizing arterial stenoses not amendable to conventional balloon angioplasty alone.