Although percutaneous brachial access has been used more often for peripheral vascular interventions (PVIs), previous studies have suggested that open brachial artery exposure for access is associated with fewer complications than percutaneous access. The present study sought to determine the incidence of complications for each access method and identify the predictors of access site complications after brachial access. The Vascular Quality Initiative national database was queried for all patients who had undergone PVI with brachial artery access from 2016 to 2019. Procedures with simultaneous thrombolysis or open procedures were excluded. The primary outcome was any perioperative brachial artery access complications. Multivariable logistic regression was used to identify any associated predictors. A total of 1400 procedures had been performed for 1242 patients; 189 procedures (13.5%) had used an open exposure. The mean patient age was 67.3 ± 9.5 years, and 55.7% of the procedures were on men. No significant demographic differences were found between the open and percutaneous groups. Open exposure procedures were more likely to have used sheaths >5F (79.4% vs 59.0%; P < .001) and treated more arteries (2.0 ± 1.8 vs 1.7 ± 0.9; P < .001) but less likely to have used multiple access sites (8.5% vs 20.1%; P < .001). Access complications occurred in 7.5% of the percutaneous procedures and 1.6% of the open exposures (P = .003). Percutaneous access was independently associated with the occurrence of brachial access complications (odds ratio [OR], 5.92; 95% confidence interval [CI], 1.76-19.9; P = .004). Other associated factors included female sex (OR, 2.23; 95% CI, 1.44-3.44; P < .001), congestive heart failure (OR, 2.02; 95% CI, 1.26-3.24; P = .003), and increasing sheath size (OR, 1.36 per each 1F increase in size; 95% CI, 1.07-1.72; P = .011); diabetes was protective (OR, 0.53; 95% CI, 0.33-0.83; P = .006). Open exposure might be advantageous compared with percutaneous access for preventing complications after brachial access. However, the difference in complications was driven by hematomas that were managed nonoperatively. Operative complications were more common in the percutaneous group, although this did not reach statistical significance. Percutaneous access should be used cautiously in women, patients with a history of congestive heart failure, those without diabetes, and interventions in which larger sheaths are required. Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.