The purpose of this study was to determine the impact of an antibiotic regimen on the incidence of empyema in patients admitted with isolated chest trauma (ISS 9/10) and hemopneumothorax requiring tube thoracostomy. All patients with isolated chest trauma and hemopneumothorax (estimated ISS 9 or 10) seen in our trauma center were considered eligible for this study. Patients were excluded for the following reasons: age less than 18 years, presence of shock at the time of initial resuscitation, ongoing antibiotic therapy for unrelated disease, documented pre-existing infection or documented abnormal immune status. Ninety patients were randomized to two treatment limbs: antibiotics and tube thoracostomy or tube thoracostomy alone. All patients had the procedure performed in the trauma center in a standard fashion. Wound care and tube care were identical. Antibiotic therapy consisted of a first-generation cephalosporin (cefazolin), one dose given just before the procedure and then q 6 h into the tube removal. Injury Severity Scores were established as described by Schwab after the manner of Baker. Statistical analysis was performed using Fisher's exact test of binary outcome. In this study, antibiotics were able to reduce the incidence of empyema in patients with isolated chest trauma and for such patients antibiotic treatment appears justified. Further work is required to determine the effect on patients with more severe injury and multisystem involvement.