Background This prospective, non-randomized study evaluated the short- and mid-term feasibility, safety, primary patency, and limb salvage of cutting balloon percutaneous transluminal angioplasty (CB-PTA) for the treatment of peripheral arterial occlusive disease (PAOD). Methods and Results All data were collected for 128 consecutive patients who underwent CB-PTA to improve infrainguinal arterial circulation between January 2003 and July 2007. One-hundred thirty-five limbs with PAOD (claudication, n = 19; critical limb ischemia [CLI], n = 116) were treated. Patency was evaluated by clinical examination and duplex ultrasonography. A total of 203 lesions (183 stenoses, 20 occlusions) were treated in 66 femoropopliteal and 69 infrapopliteal arterial segments. The TransAtlantic Inter-Societal Consensus (TASC) classification of the primary lesions was A in 41.5%, B in 45.2%, C in 8.2%, and D 5.1%. Mean follow-up was 16.1 ± 9.7 months. The overall technical success rate was 96.3% and the complication rate was 8.9%. There were two (1.5%) perioperative deaths. The primary patency rate was 82.1% at 12- and 24-months in patients with claudication (femoropopliteal lesions). The 1- and 2-year results for femoropopliteal and infrapopliteal lesions in patients with CLI were: primary patency 64.4% and 51.9 %, respectively; limb salvage 84.2% and 76.9%; survival 92.6% and 88.5%. More distal lesions and TASC classification were significant independent risk factors for outcome ( P < .05). Treatment of multiple segment lesions was an independent predictor of a favorable outcome ( P = .04). Conclusion CB-PTA is safe and feasible for the treatment of infrainguinal arterial occlusive disease, with relatively low mid-term restenosis rates compared to other endovascular treatments. However, these data cannot be extrapolated to potential outcomes for lesions >10 cm in length. Further follow-up will be necessary to evaluate the long-term results of CB-PTA.