Background The aim of the study was to investigate the clinical results of laser atherectomy in the treatment of peripheral arterial disease. Methods Retrospective analysis of consecutive patients underwent laser atherectomy at a single institution during a 7-year period by vascular surgeons and interventional cardiologists in a tertiary university-affiliated hospital. Clinical data were retrieved from patient charts and hospital electronic medical records along with the associated arteriograms. Results A total of 461 lesions in 343 limbs were treated in 300 patients with a mean age of 70 years. The indication was critical limb ischemia (CLI) with rest pain or tissue loss in 227 (66%) of interventions and claudication in 116 (34%). All procedures included an associated balloon angioplasty, while stenting was performed in 33%. Technical success was achieved in 99% with only 2 (<1%) cases with an acute procedure-related complication requiring surgical intervention. At a mean follow-up of 28 months (range, 1–87 months; median 24 months), 156 patients (45%) became asymptomatic or achieved significant clinical improvement (resolution of tissue loss or rest pain), 60 (17%) remained with CLI, 30 (9%) had a major proximal amputation, and 18 (5%) had a minor amputation. Freedom from major amputation was 90% at 5 years by life-table analysis. Univariate statistical analysis demonstrated the risk of a major amputation to be associated with diabetes, hemodialysis, and tissue loss (P < 0.05 to P < 0.005), while multivariate logistic regression analysis indicated diabetes to be overwhelmingly important (RR: 4.84; 95% confidence interval [CI]: 1.1–21.3; P < 0.05). In a similar manner, multivariate analysis indicated dialysis (RR: 2.46; 95% CI: 1.01–5.98; P < 0.05) and CLI (RR: 2.27; 95% CI: 1.42–3.65; P < 0.01) were associated with higher likelihood for lack of clinical improvement. There was no difference in major amputation rates between surgeons and interventional cardiologists (RR: 1.5; 95% CI: 0.7–2.1; P < 0.1) although it was 3 times more likely for the patients treated by surgeons to suffer from CLI (odds ratio: 3.2; 95% CI: 1.9–5.4; P < 0.0001). Conclusions Laser atherectomy is a safe and useful adjunct in limb salvage. Diabetics have much higher probability of requiring a proximal amputation, while those on dialysis and with CLI are least likely to gain clinical benefit.