Aims. In this work, the main objectives were to investigate the clinical characteristics and bacterial spectrum present in open fractures contaminated by seawater. Methods. We conducted a retrospective cohort study and included all patients with open fractures from 1st January, 2012, to 31st December, 2015, in our hospital. Patients were grouped based on the presence of seawater contamination in wounds. We compared the infection rate, bacterial spectrum, and antibiotic resistance between the two groups. Results. We totally included 1337 cases of open fracture. Wounds from 107 cases (8.0%) were contaminated by seawater. The wound infection rate of seawater-contaminated group was significantly higher in patients with Gustilo-Anderson Type II and Type III open fractures. The bacterial spectrum from seawater-contaminated wounds was remarkably different from that of the remaining. Antibiotic sensitivity tests revealed that more than 90% of infecting pathogens in seawater-contaminated wounds were sensitive to levofloxacin and ciprofloxacin. Conclusion. Cephalosporin in combination with quinolone was recommended in the early-stage management of open fractures contaminated by seawater.