Background This study determined the feasibility and potential efficacy of an evidence-based standardized smoking cessation intervention delivered by vascular surgeons to smokers with peripheral arterial disease. Methods We performed a cluster-randomized trial of current adult smokers referred to eight vascular surgery practices from September 1, 2014, to July 31, 2015. A three-component smoking cessation intervention (physician advice, nicotine replacement therapy, and telephone-based quitline referral) was compared with usual care. The primary outcome was smoking cessation for 7 days, assessed 3 months after the intervention. Secondary outcomes were patients’ nicotine dependence and health expectancies of smoking assessed using Patient Reported Outcomes Measurement Information System (PROMIS; RAND Corporation, Santa Monica, Calif). Results We enrolled 156 patients (65 in four intervention practices, 91 in four control practices), and 141 (90.3%) completed follow-up. Patients in the intervention and control practices were similar in age (mean, 61 years), sex (68% male), cigarettes per day (mean, 14), and prior quit attempts (77%). All three components of the intervention were delivered to 75% of patients in intervention practices vs to 7% of patients at control practices (P <.001). At 3 months, 23 of 57 patients (40.3%) in the intervention group quit smoking (23 of 56 patients quit who completed follow-up, plus 1 death included in the analysis in the denominator as a smoker), and 26 of 84 patients (30.9%) In the control group quit smoking (26 patients of 84 who completed follow-up, including 2 deaths included in the denominator as smokers). This difference (40.3% quit rate in intervention, 31% quit rate in control; P =.250) was not statistically significant in crude analyses (P =.250) or analyses adjusted for clustering (P =.470). Multivariable analysis showed factors associated with smoking cessation were receipt of physician advice (odds ratio for cessation, 1.96; 95% confidence interval, 1.28-3.02; P <.002) and nicotine replacement therapy (odds ratio, 1.92; 95% confidence interval, 1.43-2.56; P <.001). Conclusions Implementation of a brief, surgeon-delivered smoking cessation intervention is feasible for patients with peripheral arterial disease. A larger trial will be necessary to determine whether this is effective for smoking cessation.