Importance: Infection after cochlear implantation is a rare but serious event that can lead to meningitis. There is no consensus on prevention of infection in these patients, and each center applies its own strategy. Objective: To describe the rates of major surgical site infection for patients undergoing cochlear implantation who receive prolonged antibiotic treatment compared with those who receive a single perioperative dose of antibiotic prophylaxis. Design, setting, and participants: Retrospective cohort study of patients who underwent cochlear implantation between January 1, 2011, and July 8, 2015, with a postoperative follow-up of 1 to 3 years. In this multicenter study at 8 French university centers, 1180 patients (509 children and 671 adults) who underwent cochlear implantation during this period were included. Interventions: Prolonged antibiotic treatment vs single-dose antibiotic prophylaxis. Main outcomes and measures: Major infection and explantation. Results: Among 1180 patients (509 children [51.7% female] with a mean [SD] age of 4.6 [3.8] years and 671 adults [54.9% female] with a mean [SD] age of 54.8 [17.0] years), 12 patients (1.0%) developed a major infection, with 4 infections occurring in the prolonged antibiotic treatment group and 8 infections occurring in the antibiotic prophylaxis group (odds ratio, 2.45; 95% CI, 0.73-8.17). Children (9 of 509 [1.8%]) were more likely to develop infection than adults (3 of 671 [0.4%]). Among children, 4 infections occurred in the prolonged antibiotic group (n = 344), and 5 infections occurred in the antibiotic prophylaxis group (n = 158) (odds ratio, 2.78; 95% CI, 0.74-10.49). Among adults, 3 infections occurred in the antibiotic prophylaxis group (n = 365), whereas no infections occurred in the prolonged antibiotic treatment group (n = 290). Conclusions and relevance: After cochlear implantation, infection was rare, was less common among those who received prolonged antibiotic treatment, and was less likely to occur in adults than in children.