BACKGROUND : Infrainguinal peripheral vascular interventions (PVIs) can be performed with a variety of sheath sizes. Our aim was to investigate the effect of sheath size on postprocedural complications after infrainguinal PVIs. METHODS : The Vascular Quality Initiative (2010-2017) was queried for patients undergoing infrainguinal PVIs via retrograde common femoral artery access. Univariable and multivariable methods were performed to compare the effects of sheath size on access site complications, length of stay (LOS), and 30-day mortality. RESULTS : Of the 36,901 infrainguinal PVI procedures in the data set, the mean age was 69 years, and 59.1% of patients were male. Indications for intervention were claudication (41.6%), rest pain (13.2%), and tissue loss (45.2%). The femoropopliteal and tibial arteries were treated in 84.7% and 35.4% of cases, respectively. Interventions included stenting (39.2%) and atherectomy (21.3%). Sheath sizes of 7F, 6F, 5F, and 4F were used in 5225 (14.1%), 24,541 (66.5%), 6221 (16.9%), and 914 (2.5%) cases, respectively. Differences among sheath sizes were observed based on the ambulatory status; presence of diabetes, end-stage renal disease, previously stented ipsilateral extremities, anemia, preprocedural anticoagulation; and procedural details including indications, location of intervention, and intervention type (P < 0.001 for all). On univariable analysis, sheath size (7F vs 6F vs 5F vs 4F) was associated with differences in access site hematoma (3.5% vs 2.7% vs 2.5% vs 1.2%, P < 0.001), postprocedural LOS > 1 day (18.1% vs 25.3% vs 31.1% vs 27.9%, P < 0.001), and 30-day mortality (0.9% vs 1.4% vs 1.5% vs 1.5%, P = 0.007). There was no difference in hematoma requiring intervention or access site stenosis/occlusion based on sheath size. Multivariable analysis revealed that a larger sheath size was independently associated with access site hematoma (7F: odds ratio [OR] = 4.24, 95% confidence interval [CI] = 2.28-7.89, P < 0.001; 6F: OR = 3.11, 95% CI = 1.69-5.7, P < 0.001; 5F: OR = 2.72, 95% CI = 1.46-5.05, P = 0.002) and postprocedural LOS > 1 day (7F: OR = 1.69, 95% CI = 1.39-2.05, P < 0.001; 6F: OR = 1.5, 95% CI = 1.26-1.78, P < 0.001; 5F: OR = 1.51, 95% CI = 1.26-1.8, P < 0.001). Access site hematoma requiring intervention and 30-day mortality were not independently associated with sheath size. CONCLUSIONS : In infrainguinal PVIs, larger sheaths increased the risk of minor access site hematomas, but not major morbidity or mortality. Larger sheaths were associated with longer postprocedural LOS, possibly because of conservative management of hematomas.