The aim of this study was to define the rate of new persistent opioid use and risk factors for persistent opioid use after operative and nonoperative treatment of ankle fractures. Using a nationwide insurance claims database, Clinformatics DataMart Database, we identified opioid-naïve patients who underwent surgical treatment of unstable ankle fracture patterns between January 2009 and June 2016. Patients who underwent closed treatment of a distal fibula fracture served as a comparative group. We evaluated peritreatment and posttreatment opioid prescription fills. The primary outcome, new persistent opioid use, was defined as opioid prescription fulfillment between 91 and 180 days after the procedure. Logistic regression was used to evaluate the effect of patient factors, and the differences of the effect were tested using Wald statistics. The adjusted persistent use rates were calculated. A total of 13 088 patients underwent treatment of an ankle fracture and filled a peritreatment opioid prescription. When compared with closed treatment of a distal fibula fracture, only 2 surgical treatment subtypes demonstrated significantly increased rates of persistent use compared with the closed treatment group: open treatment of bimalleolar ankle fracture (adjusted odds ratio [aOR], 1.32; 95% CI, 1.10-1.58; P = .002) and open treatment of trimalleolar ankle fracture with fixation of posterior lip (aOR, 1.47; 95% CI, 1.04-2.07; P = .027). Rates were significantly increased (aOR, 1.56; 95% CI, 1.34-1.82; P < .001) among patients who received a total peritreatment opioid dose that was in the top 25th percentile of total oral morphine equivalents. Factors independently associated with new persistent opioid use included mental health disorders, comorbid conditions, tobacco use, and female sex. All ankle fracture treatment groups demonstrated high rates of new persistent opioid use, and persistent use was not directly linked to injury severity. Instead, we identified patient factors that demonstrated increased risk of persistent opioid use. Limiting the peritreatment opioid dose was the largest modifiable risk factor related to new persistent opioid use in this privately insured cohort. Level III, retrospective cohort study.