The efficacy of preoperative antibiotic prophylaxis in thoracic surgery with a single dose of ceftriaxone was investigated. Here we report the results of a prospective study including 192 patients undergoing thoracic surgery for non small cell lung cancer. Overall, the postoperative infection rate, as measured by wound, respiratory tract, and urinary tract infections, was 8.3% (16/192). Ceftriaxone was well tolerated, and no allergic or other adverse reactions were reported. A single preoperative dose of ceftriaxone was cost-effective and allowed considerable saving of time, material, labor costs and money. This study, even though open and non-comparative, suggests that the routine use of a single preoperative dose of ceftriaxone provides a cost-effective prophylaxis for patients undergoing major thoracic operations.