The aim of this multicentre controlled study was to analyse the effect of the timing of antibiotic administration on the preoperative prophylaxis of wound infections in contamination-prone areas of the skin and to verify the utility of a single dose of prophylactic antibiotic compared with other multiple dose schemes. A total of 527 patients were surgically treated for skin neoplasms arising in contamination-prone areas. The four prophylactic programmes, to which the patients were randomly allocated, were as follows: (A) no antibacterial prophylaxis; (B) intramuscular cephazolin, 1 g every 12 h beginning 48 h prior to surgery and continuing for 48 h after surgery; (C) intramuscular cephazolin, 1 g every 12 h beginning 2 h before surgery and continuing 24 h after surgery; and (D) intramuscular cephazolin, 1 g single dose 2 h before surgery. The rate of postoperative infections was: group A 12%, group B 4.6%, group C 0.77%, group D 2.96%. Our study confirms the utility of antibiotic prophylaxis in prevention of postoperative infections and demonstrates that brief regimens are superior to more prolonged regimens. In particular, a single dose antibiotic schedule significantly reduces the infection rate, is cheaper, and is better tolerated by the patients.