Background: Women with coronary artery disease are shown to have worse outcomes after percutaneous coronary intervention compared with men; however, less is known about sex-based outcomes following lower extremity peripheral vascular intervention (PVI) for symptomatic peripheral artery disease. The study aims to assess whether female sex is independently associated with periprocedural complications in patients undergoing PVI. Methods: Analysis includes patients undergoing lower extremity PVI from September 2016 to March 2020 from the Vascular Quality Initiative registry. Multivariate logistic regression was used to assess the independent association of female sex with post-PVI complications. Results: Of the 119 620 patients included, 47 316 (39.6%) were women. Analysis reflected that women were at higher risk of developing access site complications, including any hematoma (odds ratio [OR], 1.45 [1.35–1.57]), hematoma requiring transfusion (OR, 2.24 [1.82–2.76]; P <0.001), hematoma requiring surgery (OR, 1.49 [1.19–1.86]; P <0.001), pseudoaneurysm (OR, 1.69 [1.39–2.05]; P <0.001), and access site occlusion (OR, 1.89 [1.15–3.08]; P <0.001). Women also faced higher risks of target lesion dissection (OR, 1.36 [1.26–1.46]; P <0.001), above-knee amputation (OR, 1.37 [1.18–1.58]; P <0.001), and in-hospital mortality (OR, 1.21 [1.07–1.38]; P =0.003). Conclusions: In a contemporary cohort, women undergoing lower extremity PVI for symptomatic peripheral artery disease were at higher risk than men of developing periprocedural complications, including moderate or severe access site bleeding, above-knee amputation, and in-hospital mortality. This increased risk persisted despite adjustment for differences in baseline patient or procedural characteristics and warrants further investigation.