Background: Procalcitonin (PCT) is regarded as a specific indicator of bacterial infection. Infectious complications in patients after colorectal surgery are a common cause of morbidity and mortality. The aim of this study was to investigate a) whether PCT could serve as a negative predictive marker for postoperative complications and b) whether in patients with elevated PCT levels a preemptive treatment with the third-generation cephalosporin ceftriaxone is superior to an antibiotic treatment starting later on the appearance of clinical signs and symptoms of infection. Patients and Methods: By screening 250 patients with colorectal surgery we identified 20 patients with PCT serum levels > 1.5 ng/ml on at least 2 of the first 3 postoperative days. The remaining 230 patients were followed up for the occurrence of infectious complications. The 20 patients with elevated PCT were included in a prospective randomised pilot study comparing preemptive antibiotic treatment with ceftriaxone versus standard treatment. Results: The negative predictive value of PCT for systemic infectious complications was 98.3%. In patients receiving preemptive antibiotic treatment (ceftriaxone) both the incidence and the severity of postoperative systemic infections were significantly lower compared to those in a control group (Pearson’s c2 test p = 0.001 and p=0.007, respectively). Major differences were also observed with respect to duration of antibiotic treatment and length of hospital stay. Conclusions: PCT is an early marker for systemic infectious complications after colorectal surgery with a high negative predictive value. A significant reduction in the rate of postoperative infections in patients with elevated PCT serum concentrations was achieved by means of preemptive antibiotic treatment.