Background Clinical trial data show overall favorable outcomes of paclitaxel-eluting stents for treatment of femoro-popliteal (FP) occlusive disease. However, external validity of trial results may be restricted to less complex FP lesions, and limited data on outcomes of paclitaxel-eluting stents in real world practice have been published. Methods This is a retrospective analysis of data of all patients who received Zilver® PTX® for FP lesion from February 2013 to October 2014 at our center. The primary endpoint was primary patency, defined as peak systolic velocity ratio < 2.0 by Doppler ultrasound, or angiographic diameter stenosis < 50%, or freedom from clinically driven target lesion revascularization. Results Seventy-eight patients received Zilver® PTX® for FP lesions in the pre-specified time period. Of them, 63 had follow-up data and were included in this study. Mean patient age was 66.3 ± 9.4 years, and 57.1% of the patients were men. Participants had a high prevalence of diabetes (49.2%), hypertension (93.7%), hyperlipidemia (93.7%), previous coronary revascularization (52.4%), or previous peripheral arterial disease (77.8%). Critical limb ischemia was present in 25.4% of the patients, Trans-Atlantic Inter-Society Consensus (TASC) class C or D in 76.2%, in-stent restenosis (ISR) in 36.5%, and total occlusion in 69.8%. Mean lesion length was 218.9 ± 128.3 mm, mean number of stents was 2.02 ± 1.0, and total stent length was 189.0 ± 128.5 mm. Mean follow-up was 270.4 ± 190.3 days. Primary patency rate at 1 year was 66.7% by Kaplan–Meier survival curve. When compared with patients with primary patency at follow up, those with an adverse outcome had higher prevalence of TASC II class C or D lesions (100% vs. 68.8%, p = 0.013), and were more likely to have ISR (66.7% vs. 27.1%, p = 0.012), longer lesion (291.3 ± 138.7 vs. 195.7 ± 117.1, p = 0.011), and incomplete coverage of the lesion (full coverage of lesions: 40% vs. 77.1%, p = 0.011). Conclusion Post marketing use of Zilver® PTX® for the treatment of FP lesions is associated with lower patency rates compared with clinical trial data. This may be related to the high prevalence of TASC II class C or D lesions and ISR in real world practice. Future studies should be more representative of contemporary clinical practice.