Introduction The aim of present study is to investigate the most common infection pathogen found in the postoperative wounds, following surgical treatment of oral and oropharyngeal cancer, in order to identify the most suitable antibiotic treatment. Patients and methods We analyzed patients with squamous cell cancer of oral and oropharyngeal region. In patients who developed postoperative wound infection, wound swabs were taken from three different sites: the cannula, wounds on the neck and wounds in the oral cavity. Results In total 195 patients were included. The postoperative wound infection was detected in 115 patients (59%). In average, the swabs were taken 8 days after the surgery. The similar bacterial species from all three sites were detected in 24 patients (12, 3%). In comparison, we found that there was statistically significant difference in the bacteria abundance from all three sites (p=0, 031). There were significantly more bacteria in the wounds of the neck than cannula (p=0, 007) and in the wounds in the oral cavity than cannula (p=0, 002). No statistically significant difference between the wound on the neck and in the oral cavity was found. The most frequently isolated bacterial family was Enterobacteriaceae. Other more commonly isolated bacteria species were Staphylococcus spp. (G+), Pseudomonas aeruginosa (G-), Corynebacteruim spp. (G +) and Acinetobacter baumanii (G-). Conclusion Based on the most commonly isolated groups of pathogens we concluded that probably the best empiric antibiotic treatment of wound infections until antibiogram is completed might be achieved from the group of aminoglycosides or quinolones. Antibiotic therapy should be reviewed if necessary when antibiogram is completed.