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Infection remains a serious complication after surgical produces. The main risk factors for developing infection are: 1. endogenous-host related, 2. exogenous-produce related, 4. environmental-related ones. Systemic antibiotic prophylaxis significantly reduces the incidence of potentially serious infective complications. It is indicated in procedures with incidence of infective complications more as 5%, in clean contaminated wounds and also in produces, in which infection has fatal consequences (vascular surgery, heart surgery, traumatology). The decision to use antibiotic prophylaxis depends upon the operation to be performed, the findings at operations, the general health of the patient and pharmacological and antibacterial properties of the agent. Timing of the first dose (administration not more as 1 hour preoperatively) and duration not more as 24 hours are very important. We use the second generations of cephalosporins (cefuroxim and after antibiotic rotation cefamandol) in antibiotic prophylaxis obligatory in vascular surgery, pacemaker implantation, traumatology and in colorectal surgery (there in combination with metronidasol) with mean infection rate in clean surgical procedures from 0.5 to 1.5%. Complications after antibiotic prophylaxis are very rare. However antibiotic prophylaxis can not compensate the correction of medical problems preoperatively and the meticulous surgical technique.