The optimal duration of antibiotic therapy for fracture-related infection (FRI) has not been well defined. Our aim was to assess the recurrence rate of infection in patients who underwent six, 12, or 24weeks of antibiotic therapy following surgical treatment for FRI one year after antibiotic discontinuation. Additionally, complications were monitored. Patients with FRI underwent surgical treatment, and antibiotic therapy was initiated. The patients were divided into groups at the 6th and 12th weeks of antibiotic therapy. The primary endpoint was the recurrence of deep or superficial infection at 90days and one year after the end of antimicrobial therapy. There was no difference in the recurrence of infection 90days or one year after stopping antibiotic therapy among patients treated for six, 12, or 24weeks (p = 0.98 and p = 0.19, respectively). The overall recurrence rate of infection 90days after stopping antibiotic therapy was 4.9% (8/163), and one year after discontinuation of antibiotic therapy was 9.8% (16/163). There was a statistically significant difference in the incidence of adverse effects among the three groups (chi-square; p = 0.01). Adverse effects were more common in the group treated for 24weeks than in the groups treated for 6weeks (z score, p = 0.017) or 12weeks (z score, p = 0.005). Antibiotic therapy longer than 6weeks did not reduce the recurrence of FRI after one year of follow-up. Additionally, antibiotic treatment for 24weeks increases adverse events such as skin reactions and acute renal failure.