The main interests covered in this article are the determination of risk factors and incidence of surgical site infections in dermatosurgery and suggestions for rational use of antibiotic prophylaxis. A total of 3284 consecutive dermatosurgical interventions in 1088 patients were performed in our dermatosurgery department. Data regarding patient characteristics and perioperative course were prospectively collected and retrospective analysis of this data was performed. Association of perioperative parameters and postoperative surgical site infections was assessed by χ2-test. Rate of postoperative infections in our study was low (1.9%). Purulent surgical sites showed the highest incidence of severe postoperative infections (4.7%; P < 0.001). The lowest incidence of mild infections was seen in preoperatively clean surgical sites (0.8%; P < 0.001). All patients with severe infections and 68% patients with mild infections were older than 70 years. The head and neck and acral regions were the groups mostly affected by mild postoperative conditions (2.4% and 1.7%, respectively; P = 0.006). The frequency of mild and severe infections in procedures performed by experienced surgeons was lower than in procedures performed by less experienced surgeons (0.6% vs 3.1% in mild infections, 0.1 vs 0.8 in severe infections; P < 0.001). The main risk factors for postoperative infections were wounds in the head and neck region, lips and oral mucosa or acral regions, older age of patients, worse preoperative state of surgical sites and less experienced surgeons. In the majority of cases where risk factors were missing there was no need of antibiotic prophylaxis.