The aim of this study was to investigate whether an extended course of prophylactic antibiotic could reduce the wound infection rate in a subtropical country. Fifty-three consecutive cases scheduled to receive major head and neck operations were randomised into one-day or three-day prophylactic antibiotic groups. Thirteen cases (24.5 per cent) developed wound infections after operations. The duration of prophylactic antibiotic was not related to the surgical wound infection. However, pre-operative haemoglobulin less than 10.5 g/dl (odds ratio: 7.24, 95 per cent confidence interval: 1.28-41.0) and reconstruction with a free flap or pectoris major myocutaneous flap during the operation (odds ratio: 11.04, 95 per cent confidence interval: 1.17-104.7) were associated factors significantly influencing post-operative wound infection. Therefore, one day of prophylactic antibiotic was effective in major head and neck procedures but should not be substituted for proper aseptic and meticulous surgical techniques.