Perioperative antimicrobial prophylaxis (PAP) involves administration of antimicrobial agents (AMA) to patients undergoing a surgical intervention and aims to reduce the risk of postoperative infectious complications, especially at surgical sites. In the present work we assess efficiency and safety of AMA used for prevention of postoperative infectious complications. In the course of our study we pre-analyzed 576 medical histories of post-op patients aged 18 to 87 years (mean age М ± SD was 57.4 ± 14.5 years), of which 347 (60.2%) were male and 229 (39.8%) female. Only 481 histories were selected for final analysis. We assessed the choice of antibacterial therapy, the frequency of adverse reactions (AR) and infectious complications and the type of the latter. PAP regimens were consistent with the official guidelines in 207 (43.04%) cases. PAP recommendations were ignored in 274 cases (56.96%), and the timing was wrong in 364 cases (75.7%). Incorrect dosages were administered in 225 cases (46.8%). We also discovered an association between irrational PAP regimens and 1) the length of patient’s stay in the intensive care unit (р = 0.003 and р < 0.005), 2) the frequency of reoperations associated with infection (р = 0.001), 3) mortality rates (р = 0.002), and 4) isolation of strains with multidrug resistance (р = 0.016). We conclude that PAP regimens for the inpatients of surgical wards are often compromised by failure to comply with the official guidelines, wrong timing and incorrect dosage, which negatively affects hospital statistics.