Background/aimCompound or open depressed fractures (CDF) is one of the urgent operations of neurosurgery, as it can result in complications of infection. This study is reported to investigate the effect of topical vancomycin powder to the infection rates in the compound depressed skull fractures which have been operated on. Materials and methodsThis present study was conducted on 46 cases with compound depressed skull fractures which have been operated on. Cases were divided into two groups according to the use of subgaleal topical vancomycin powder during the operation. The preoperative and postoperative CRP levels, localization of the fracture, hospitalization time, operation length, dural injury, pneumocephalus, and mortality rates have been examined. ResultsIn cases with dural injury and pneumocephalus, a statistically significant relationship was found between the use of topical vancomycin powder and the frequency of post-op infection (p < 0.001). It was observed that the incidence of postoperative infection was significantly higher in 12 (85.7%) cases with pneumocephalus and dural injury when vancomycin powder was not used. Also, it was observed that the post-operative infection level was significantly higher in fractures in the frontal and parietal regions without vancomycin powder(p < 0.05). ConclusionsThe use of subgaleal topical vancomycin powder is an option to reduce the infection rates and mortality, especially in the cases of compound depressed fractures, which is considered as a dirty wound and prone to infection. It is especially recommended in the presence of dural injury and pneumocephalus.