Surgical site infections are still considered a major health problem, having a negative impact on the well-being of the population, increasing morbidity and duration of postoperative rehabilitation of patients. Beyond the consequences of SSI associated with patients, the medical system is also affected, recording an excessive use of both material and human resources, solution to these problems being a rational antibiotic prophylaxis based on certain principles. The aim of the study was to identify the principles of correct prophylaxis with antibacterial drugs in surgery and to appreciate the correctness of the administration of antibiotics for prophylactic purposes, in particular: choosing the right drug, pre-/intraopertive antibiotic timing and duration of prophylaxis. To choose the right drug its necessary to take into account the microbial flora involved with prevalence in a certain type of surgery (especially staphylococci which cause about 80% of postoperative purulent complications) and its sensitivity to some groups of antibiotics, but in most cases, penicillins or cephalosporins are predominantly used, but if the patient is colonized with MRSA, solution is vancomycin. The ideal antibacterial effect is obtained when the concentration of the drug in the tissues exceeds the minimum inhibitory concentration, and its level is maintained throughout the entire surgery. In most cases, a single therapeutic dose of antibiotic is sufficient for antimicrobial prophylaxis. For most surgeries, it is optimal to administer antibiotics intravenously 30-40 minutes before surgery, because in half an hour the serum and t concentration are equal, only vancomycin and fluoroquinolones must be administered 120 minutes before incision because of their longer half-life. Although prophylaxis with a single dose of antibiotic is usually sufficient, there are cases in which readministration of an additional dose over a period of time is essential, this being twice the half-life of the drug. However, the duration of prophylaxis for all procedures should not be longer than 24 hours. Only in the cases like cardio-thoracic surgery prophylaxis lasts more than 24 hours but not more than 48 hours. The rational use of antibiotics for prophylactic purposes will have a major impact on contemporary medicine. Selection of drugs by principles according to guidelines will reduce the rate of SSI, microbial resistance to antibiotics and the costs of hospitalization of patients.